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MRCPCH Part 2:
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Ill
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Kate H. Creese MB Bch ocH DRcoc MRCPCH

Specialist Registrar in Paediatrics
Depart1nent of Paediatrics
University Hospital of Wales
Cardiff, UK
Colin V.E. Powell MBchB ocH MRCP FRACP FRCPCH MD

Consultant Paediatrician
Department of General Paediatrics
Children's Hospital of Wales
Cardiff, UK
Patrick H.T. Cartlidge DM FRCP FRcPcH

Senior Lecturer in Child Health and Honorary Consultant Paediatrician
Departm.ent of Child Health
University Hospital of Wales
Cardiff, UK
Edinburgh London New York Oxford Philadelphia St Louis Sydney Toronto 2008
CHURCHILL
LIVINGSTONE
ELSEVIER
CHURCHILL LIVINGSTONE An imprint of Elsevier Limited
© 2008, Elsevier Limited. All rights reserved.
The rights of Kate H Creese, Colin VE Powell and Patrick HT Cartlidge to be identified as
authors of this work has been asserted by them in accordance with the Copyright, Designs
and Patents Act 1988
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First published 2008
ISBN: 978-0-443-10166-3
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Notice
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Chapter 1 Case 1.1 - Case 1.20
Chapter 2 Case 2.1 Case 2.20 43
Chapter 3 Case 3.1 - Case 3.19 85
Chapter 5 Case 5.1 Case 5.24 167
Index 421
vii
A male infant was born at 28 weeks' gestation weighing 940 g. He was ventilated for
16 days because of respiratory distress syndrome. He is now 25 days old and has been s:
;x:,
stable since extubation. He is in air and on full enteral feeds with a preterm neonatal ()
formula. '"O
()
I
You are asked to see him because he has developed an increased respiratory rate and '"O
intermittent self-limiting apnoeas. OJ
�
On examination his temperature is 37.9 °C, heart rate 192 bpm and respiratory rate 78 N
breaths/min. He has cold hands and feet and a capillary refill time of 3 s over the
sternum. He has good chest movement and mild sub-costal recession. Air entry is good
and his chest is clear. The heart sounds are normal but he has a 2/6 short systolic
murmur at the left sternal edge. The abdomen is distended and the bowel sounds are
not heard. The liver is palpable 1 cm below the costal margin; there is no other
organomegaly.
a. What three investigations would you initially carry out?
SELECT THE THREE MOST APPROPRIATE ANSWERS
i. CXR
ii. Blood culture
iii. Lumbar puncture
iv. AXR
v. Cranial ultrasound scan
vi. FBC
vii. Echocardiogram
viii. ECG
ix. Coagulation screen
b. What is the most likely diagnosis?
SELECT ONE ANSWER ONLY
i. Group 8 streptococcal sepsis
ii. Fungal sepsis
iii. Pulmonary hypertension
iv. Necrotising enterocolitis (NEC)
v. Meningitis
vi. Pneumonia
vii. lntraventricular haemorrhage
3
1
a. ii. Blood culture
iv. AXR
,0
C vi. FBC
(I)
� b. iv. Necrotising enterocolitis (NEC)
o·
:J This picture in a premature neonate could be any systemic sepsis but NEC is the
V)
OJ
n10st likely. Initial investigations should include an AXR, FBC, and blood culture.
:J Other investigations indicated would be serurn U&E, blood glucose and blood gas. A
0..
CRP may be helpful. AXR may show intranrnral gas, gas in the portal vein, free gas,
)>
:J dilated or thickened bowel loops and a FBC may shm:v thrombocytopaenia and/or
� neutropaenia.
�
V) Management in this case involves m,ygen, a bolus of 20 ml/kg albumin or 0.9% sodiun1
-h
0
-,
chloride, stopping enteral feeds and con1mencing i.v. maintenance fluids. Broad
r+ spectrurn_ antibiotics, e.g. cefotaxime and metronidazole, according to local protocol,
::::,
(D should also be given.
z
(D
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3
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3
4
Fig 1.2
A 3-year-old girl presents with a fever 2 weeks after a 3-months stay with relatives in
Africa. She is not eating and has lost weight. She has developed a cough. On
examination she is pyrexial, has generalised lymphadenopathy and a palpable spleen.
The CXR is shown (see Fig. 1.2).
Blood tests show:
Hb11.3 g/dl
wee
12.4 x 109 /I
Platelets 244 x 109/I
Malaria slide negative
a. What are the main differential diagnoses to consider?
SELECT TWO ANSWERS ONLY
i. a 1-antitrypsin deficiency
ii. Wegener's granulomatosis
iii. Lyme disease
iv. Miliary tuberculosis
v. Lymphoma
vi. Kawasaki disease
b. What investigations could help to c_g_nfirm the diagnosis?
i. Blood culture
ii. ELISA for B. burgdorferi antibodies
iii. Bone marrow
iv. CT chest
v. Mantoux/Heaf test
vi. Urinalysis
5
TO CASE 1.2
a. iv. Miliary tuberculosis (TB)
v. Lymphoma
D b. 111. Bone marrow
C
(I)
v. Mantoux/Heaf test
!!}.
o·
:J
The X-ray shows typical features of miliary TB: widespread lung infiltrates, giving a
VI
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'snowstorm' appearance. Other features suggesting 1niliary TB but not shown on this
::l CXR are hilar lymphadenopathy and lobar infiltrates.
Cl.
)> Although the history and examination are suggestive of lymphoma, the CXR does not
::l
show the expected bilateral hilar ly111phadenopathy. Neither TB nor lyn1phornas would
�
(I) show diagnostic changes on blood count. Malaria cannot be excluded on a single thick
'""'I
VI
and thin film, at least three should be pe1for111ed if there is a real clinical suspicion.
-I-,
Q TB can be suspected with a positive Mantoux/Heaf test in the absence of BCG

,-+
::::; vaccination, but may be falsely negative. Sputum and gastric aspirate cultures for
(I)
mycobacteria 111.ay also be falsely negative, and a result can take up to 6 weeks. Biopsy
z
(I) of the liver or bone marrow with appropriate staining can often yield an early diagnosis.
�
.,,
0
Similarly, the histology of biopsied lymph nodes would confirm_ a diagnosis of
lymphoma.
3
OJ In this case, the patient had a weakly positive Mantoux, and responded dramatically
,-+
m to anti-tuberculous therapy, 1naking a biopsy unnecessa1y. Mycobacterium tuberculosis
>< was cultured from gastric aspirates and full sensitivities were obtained 5 weeks after
QJ
3 therapy was cornrnenced.
6
A baby boy was admitted to the neonatal unit because of prematurity (35 weeks'
gestation) and low birth weight (1700 g). He was commenced on nasogastric formula
feeds which were gradually increased in volume to 150 ml/kg per 24 h by day 4. He
s:
:,;:,
()
remained alert and active and was tolerating feeds well without any vomiting but was ""O
()
noted to have lost more than 10% of birth weight so his feeds were increased to I
200 ml/kg per 24 h by day 6. At the age of 8 days, he had lost 20% of birth weight ""O
a,
and appeared dehydrated. A blood gas taken at this point showed: ;::i
pH 7.07 N
pCO 2 2.18 kPa
Base excess -25 mmol/1
Blood glucose 63 mmol/1
What is the most likely diagnosis?
i. Neonatal diabetes mellitus
ii. Transient neonatal insulin resistance
iii. Medium chain acyl Co-A dehydrogenase deficiency
iv. lnsulinoma'/
v. Congenital pancreatic agenesis
vi. Fatty acid oxidation defect
7
1.3
i. Neonatal diabetes mellitus
,0 This baby has neonatal diabetes mellitus. This is a rare condition ,vith an incidence of
C
(I)
approximately 1 in 400 000 in the UK. Babies present ,vith intrauterine growth retarda
VI
tion, followed by severe failure to thrive, hyperglycaemia and dehydration within the
o·
,-+
:::s
first 6 weeks of life.
VI
OJ In n1ost babies the condition is transient and resolves at a median age of 3 months;
:::s
0. however, they are at a higher risk of type II diabetes later in life. An abnormality of
)> chromosome 6 can be identified in most fan1ilial cases and in 70% of sporadic cases.
:::s
Many of the sporadic cases are due to paternal uniparental disomy of chromoson1e 6
�
(I) (i.e. both inherited from_ the father) or due to duplication of part of chromosome 6q.
""'I
VI Identification of the child's genotype can now help predict whether the diabetes will
-h
0
""'I
be permanent.
,-+
:::,
(I)
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(I)
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0
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3
8
A female infant was born at term by normal delivery following a pregnancy that was
uneventful apart from an influenza-like illness 2 weeks prior to delivery. She became s:
:::0
unwell soon after delivery. Persistent pulmonary hypertension of the newborn was ri
diagnosed and she was treated with high-frequency ventilation and nitric oxide therapy. -0
n
She responded well and was extubated after 5 days. She commenced enteral feeds on ::r:
the 4th day of life and achieved full feeds on day 9. She was noted to have progressive -0
OJ
.....
jaundice from the 10th day onwards. Other examination findings included a large broad r+
forehead, a straight pointed nose, deep-set eyes, a soft systolic murmur, and N
hepato-splenomegaly.
a. What is the probable diagnosis?
i. cx1-antitrypsin deficiency
ii. Alagille syndrome
iii. Biliary atresia
iv. Wilson's disease
v. Neonatal cholestasis
vi. DiGeorge syndrome
b. What deficiency is this child at risk of and how would you prevent it?
i. T cells
ii. Chymotrypsin
iii. Folate
iv. Fat-soluble vitamins
V. lgG
vi. Iron
9
ANSWERS TO 1.4
a. ii. Alagille syndrome
b. iv. Fat-soluble vitamins
0
C
Four major categories of differential diagnosis are suggested by the initial history:
�
(I)
a·
::I
1. congenital viral infection
2. bacterial sepsis, e.g. group B streptococcal infection
VI
Q)
3. inherited metabolic disorders, e.g. galactosaen1ia
::I 4. biliary obstructive disorders, e.g. biliary atresia - extrahepatic and intrahepatic (e.g.
a.
Alagille syndrome)
)>
::I
However, the dysmorphic features suggest Alagille syndrome. Information about stool
(I) and urine colour would be helpful, and total and direct serum bilirubin concentration
"""I
VI should be checked. A liver biopsy shovving bile duct hypoplasia would help confirm
-
0
"""I
the diagnosis and other investigations would need to be done to look for associated
r+ conditions:
::::r
(I) echocardiography (pulmonary stenosis/septal defect)
z • radiographs of the vertebrae (vertebral anomaly)
(I)
eye examination (posterior en1bryotoxin and optic nerve drusen)
"TI DNA analysis OAG1 gene mutation)
0
3
Q)
Fat malabsorption secondary to chronic cholestasis is associated with a risk of fat-soluble
r+ vitamin deficiency (A, D, E, K). Fat-soluble vitamin supplementation, se1ni-ele1nental
m milk formula and MCT supple1nentation are required. Neurological sequelae of vitamin
><
Q) E deficiency may occur despite treatment.
3
Alagille syndrome (arteriohepatic dysplasia) is a dominantly inherited disorder charac
terised by paucity of intra-hepatic bile ducts, with resultant liver disease, along v,rith
cardiac, skeletal and ocular abnormalities and characteristic facial features. Approxi
mately 70% of patients have mutations of Jagged 1 OAG 1) gene (mapped to 20p12).
Mortality is variable; most die of liver disease, heart disease or infections. An estimated
50% of patients require transplantation by the age of 19, due to cirrhosis, pruritus or
osteodystrophy. There is an increased risk of malignancy in patients with Alagille syn
drome and cirrhosis.
Physical signs may include:
growth retardation (proportionate short stature)
prominent forehead/frontal bossing
• deep set eyes
• hypertelorism
posterior ernbryotoxon in the anterior chamber of the eye
pron1inent nasal bridge
peripheral pulmonary stenosis
signs of hepatic dysfunction, e.g. jaundice and scratch n1arks from pruritus
vertebral arch defects (hemivertebrae, butterfly vertebrae)
rib anomalies
hypogonadism
Associations include:
renal anomalies
hypoglycaemia
mild mental retardation in about 15% of cases
pancreatic insufficiency
10
A term infant was born by normal vaginal delivery with an Apgar score of 6 at 1 min
and 9 at 5 min. After 10 min, he was noted to be dusky and floppy. His arterial gas s:
;o
showed pH 7.14, pCO2 10.3 kPa, pO2 2.4 kPa, and BE -6.2. He was ventilated and ri
treated for sepsis. He required pressures of 14/4, rate of 20/min and FiO2 of 0.21. He ""O
ri
was still ventilated 6 days later. Three attempts at extubation failed. He also showed :c
frequent dysrhythmias in the form of bradycardia on the ECG monitor. On examination, ""O
OJ
he was active and moving all limbs normally. �
N
a. What is the most likely diagnosis?
i. Hypoxic ischaemic encephalopathy
ii. Laryngomalacia
iii. Overwhelming sepsis
iv. Congenital heart disease
v. Congenital central hypoventilation syndrome
b. What are the investigations for this diagnosis?
SELECT THREE ANSWERS ONLY
i. Echocardiogram
ii. Muscle biopsy
iii. CSF analysis
iv. Creatinine kinase
v. Lung biopsy
vi. MRI brain
vii. CXR
viii. FBC
11
.5
a. v. Congenital central hypoventilation syndrome
b. ii. Muscle biopsy
D vi. MRI brain
C
(I)
vii. CXR
�
o· The rnost likely diagnosis is congenital central hypoventilation syndrome. Causes
::::,
V,
0)
include myopathies, myasthenia gravis, diaphragmatic dysfunction, a structural hind
::::, brain or brainstem abnormality and Moebius syndro1ne.
0..
)> Investigations include a rnuscle biopsy, a CXR, fluoroscopy of the diaphragn1, 24-h
::::,
continuous ECG monitoring, and MRI of the brain and brainstem.
�
......
(I)
V,
Management involves careful observation of the infant's tidal volume and respiratory
-+, frequency responses to the endogenous challenges of hypercarbia and hypoxaen1ia, both
0
...... whilst avvake and during sleep. The distinction between the need for artificial ventila
rl
::r tory support only during sleep, or while awake and asleep, should be made after several
(I)
detailed evaluations.
z
(I)
� Following confirmation of the diagnosis, an experienced paediatric otolaryngologist

,,
0
should perform_ a tracheostomy. A transition to a home mechanical ventilator should
3
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be made whilst the child is an inpatient to allow ample time for parental training before
discharge.
ri-
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><
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12
Fig 1.6
A 13-week-old infant presents because his mother noticed that his head had become
larger. His head circumference had crossed from the 75th centile to the 99.6th centile
over the previous 4 weeks. His fontanelle was widely open and full, but otherwise he
was well and there was no history of trauma. The cranial CT scans are shown.
What do the CT scans show?
Cerebral atrophy
Left posterior fracture
Bilateral subdural collections
Post-haemorrhagic ventricular dilatation
,, . Cerebral oedema
Bilateral extradural collections
13
TO CASE 1.6
ii. Left posterior fracture
iii. Bilateral subdural collections
0
C:
(1) The CT scans show bilateral hypodense subdural collections overlying both cerebral
!!l hernispheres. Posteriorly, there is fresh subdural blood extending to the right. There is
o·
:J also a left posterior fracture; this is widened and the anterior aspect has a sclerotic
V'l
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margin suggesting a degree of healing. The appearance of the scan suggests haernor
:J rhages of two different ages.
c..
)> A full clinical history and examination should be taken, and a skeletal survey, bone
:J
scan, FBC and coagulation profile, metabolic screen for glutaric aciduria, and ophthal
� mological consultation should be arranged. A referral to social services needs to be
�
(1)
V'l made.
-+,
Q This child v-1ould need adn1ission, consultation with the neurosurgical team_, and the
,-+
:::r consultant paediatrician on duty and/ or the consultant responsible for child protection
(1)
must be infonned, as well as the trust officer for child protection. Social services need
z
(1) to be contacted in order to initiate enquiry and family assessn1ent. The general practi
:§: tioner needs to be informed, and a case conference needs to be organised. The CT
-n
0 scan showed two haemorrhages of different ages along with the skull fracture which
3OJ \Vas starting to heal. The most likely diagnosis is child abuse. Sequelae of shaking an
,-+ infant include intracranial trauma which may be life threatening, retinal haemorrhage,
m
><
lin1b and rib fractures. A skeletal survey n1ay include X-rays, a radioisotope bone scan
OJ and a CT brain scan if indicated, and may reveal fractures of varying ages. Other
3 explanations should be sought, such as accidental trauma, a coagulopathy or glutaric
aciduria type 1, which can be associated with subdural haen10rrhages. Child protection
investigation should be initiated. A doctor with expertise in child protection should
undertake the latter in conjunction \Vith social services.
14
A 16-year-old boy was referred by his GP with atypical absence seizures. A cranial CT
scan showed multiple areas of intracranial calcification. He had been well controlled on s.:
.,,
vigabatrin for 6 years. Over the last 2 years, he had had increasing difficulty with ::0
(')
concentration, literacy and numeracy skills, requiring considerable support.
(')
.,,....
I
Investigations were as follows:
Woods light examination normal 0,
r+
Renal ultrasound scan normal
N
Echocardiogram normal
Ophthalmology assessment visual field loss, visual acuity satisfactory.
i. CMV infection1
ii. Tuberose sclerosis complex (TSC)
iii. Congenital toxoplasmosis infection
iv. Rett's syndrome
v. West syndrome
15
1.7
ii. Tuberous sclerosis complex (TSC)
TSC is a nmltisystern disorder affecting between 1 : 5000 and 1 : 10 000 nevvborns. It
can present at any age fron1 the antenatal period into adulthood, with considerable
variation in severity. It results from_ a mutation on chromosorne 9 or chromosome 16.
Although the condition is autosomal dominant, 60-70% of cases are sporadic and rep
resent new n1utations.
Seizures occur in 65% of patients with TSC, often presenting in infancy as infantile
spasms. Seizure control can be difficult. The complete remission of fits is less common
with TSC than with idiopathic epilepsy. Vigabatrin may cause visual field defects,
although current evidence suggests that it is beneficial in the initial rnanagement of
infantile spasms or uncontrolled epilepsy. Developmental delay occurs in up to 60% of
children, learning difficulties being greatest in those presenting with infantile spasms.
Control of the epilepsy may help with attention as ,veil as psychiatric and behavioural
difficulties. Children are also at increased risk of developing a subependymal giant cell
astrocytoma* (5%) in late childhood. Calcified subependymal nodules* are found in
80% of cases of TSC. Cardiac rhabdomyomas* are common in neonates but rarely
,,
0
cause complications. These decrease in mass after birth. Arterial aneurysms can also
3OJ occur. Skin lesions consist of facial angiofibrornas*, periungal fibromas*, shagreen
patch*, fibrous plaque on the forehead* and hypomelanic (ash leaf) macules*.
,-+
m
><
Renal complications include angiomyolipomas* (80%), polycystic kidney disease (20%)
OJ and renal cell carcinoma (1%). Pulmonary lymphangioleiomyomatosis* is rare and
3 occurs exclusively in females, usually presenting in adulthood with respiratory
impairment.
16 *A definitive diagnosis of TSC requires t,vo of these major features.

s:
::::0
(')
--0
(')
I
--0
Ill
;::i
N
Fig 1.8
This is an X-ray of a term baby taken at 1 h of age. The birthweight was 4495 g.
What should be specifically checked on initial examination?
1 Presence of a distal pulse
Associated fracture of the clavicle
Associated nerve injury (palsy)
1v. Blood sugar
v. Moro reflex
17
ANSWER CASE 1.8
i. Presence of a distal pulse
D The X-ray shows a 1nid-shaft spiral fracture of the left humerus with around 60 ° of
C:
(I)
angulation. This was sustained during delivery (shoulder dystocia). Limitation of passive
� motion due to pain and crepitance will be present. The exan1ination should include
o· an assessment of n1otor function and a check for the presence of a distal (radial) pulse.
:::::i
Vl
OJ
This injury can be associated with radial nerve injury leading to vvrist drop and inability
:::::i to extend the fingers at the metacarpophalangeal joints. The differential diagnosis ·will
Q..
include brachial plexus injury or fracture of the clavicle. The former will present as
)>
:::::i either Erb's, Klmnpke's or Erb-Duchenne-Klumpke palsy.
�
ro M�nagement involves ensuring adequate analgesia and supporting the affected arm, for
'"'I
Vl example with the use of a net bandage against the chest 'Nall to immobilize in flexion
-h
Q at the elbow.
,-+
:::::i The fracture is likely to unite within 2 weeks despite the angulation ,vithout any
ro
operative intervention and the long-term outlook is good. Angular deformities will be
z
ro spontaneously corrected with growth.
�
.,,
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3
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,-+
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3
18
A 7-year-old girl presented with a 2-month history of unexplained episodes of pyrexia.
In that period she had also developed widespread lymphadenopathy and had had one $'.
nose bleed which had stopped spontaneously. On examination she was pale with :::0
{')
palpable lymph nodes in the cervical, pre-auricular and inguinal regions. She also had '"O
{')
an enlarged liver and spleen. A peripheral blood count and film showed: I
Hb 7.4 g/dl '"O
wee
Q)
6.3 x 109/1 ;:::i.
Neutrophils 0.5 x 109/I N
Blasts 20%
i. Aplastic anaemia
ii. Non-Hodgkin's lymphoma
iii. Acute lymphoblastic leukaemia
iv. Fanconi's anaemia
v. Acute myeloid leukaemia
b. What features of this condition signify a favourable prognosis?
i. Age>1 year
ii. Male sex
iii. High white count
1v. Age <10 years
v. Low white count
19
ANSWERS TO 1.9
a. iii. Acute lymphoblastic leukaemia
b. i. Age >1 year
0 v. Low white count
C
(I)
� The likely diagnosis in this girl is acute lymphoblastic leukaemia. Features that signif),
c:5' a favourable prognosis include age > 1 year and under 10 years, female sex and a lmv
:::l
V'l
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v.rhite count.
:::l
Cl. Patients with high ,vhite counts and, therefore, large tumour mass are at risk of tumour
)> lysis syndrome once chemotherapy starts. To minimise the effects of large quantities of
:::l
intracellular ions (such as uric acid and phosphate) being deposited in the kidneys and
�
(I) causing renal failure, patients should receive hydration (3 1/ni /24 h) and allopurinol
for approximately 12 h before treatment starts.
--h
�
r-+
::::;
ro
z
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r-+
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3
20
1. Staphylococcal scalded skin syndrome
2. Rubella
3. Measles s:
:;;t1
4. Kawasaki disease (i
'1:1
5. Impetigo (i
I
6. Scarlet fever
'1:1
7. Infectious mononucleosis ....
0)
..+
8. Still's disease N
9. Roseola infantum
10. Erythema infectiosum
For each of the following case scenarios select the most likely diagnosis from
the list above.
a. A 5-year-old boy has a bright red, punctate erythematous rash which blanches on
pressure. It seemed to begin in the axillae associated with some perioral pallor and
relative facial sparing. The skin feels like 'sandpaper'. The rash fades and
desquamation occurs on the hands and feet. A thick white exudate develops on the
tongue which peels leaving a bright red 'raspberry tongue' with prominent papillae.
A salmon-coloured, reticulate macular rash develops mainly over the extensor
surfaces of the limbs in a 5-year-old boy with a swinging temperature; he is also
complaining of hot, swollen, painful knees and left elbow and on examination is
found to have a palpable spleen. Investigations reveal an ESR of 95, although the
FBC, CRP and CXR are normal.
c. A 4-year-old girl presents to her general practitioner with a 1-day history of a high
fever, associated with the appearance of a discrete, maculopapular rash, which was
first noted on the face and neck. She had been unwell for 3-4 days previously with
upper respiratory tract symptoms and conjunctivitis.
21
1.10
a. 6. Scarlet fever
D
C
(I)
Scarlet fever occurs when the infectious organism (usually a group A streptococcus)
V\
produces erythrogenic toxin in an individual who does not possess neutralizing anti
o·
r+
:::i
toxin antibodies. The incubation period is 2-4 days following a streptococcal infection,
V\
OJ
usually in the pha1yn,'C. The rash, initially on the neck, appears around day 2, and
:::i quickly becomes punctate and generalised. It is prominent in the flexures, but typically
Q..
spares the face, palms and soles. The rash lasts about 5 days, and is followed by desqu
)>
:::i amation of the skin. The face may be flushed but characteristically with circumoral
pallor. Early in the disease the tongue has a white coating through which pron1inent
(I)
'""I
V\
bright red papillae can be seen ('strawbeny tongue'), but this coating later disappears,
-+, leaving a raw-looking red colour ('raspbeny tongue'). Complications include peritonsil
O ·
'""I lar or retropha1yngeal abscesses and otitis n1edia.
r+
::;
(I)
b. 8. Still's disease (systemic onset juvenile chronic arthritis)
z
(I)
Still's is the commonest type of juvenile chronic arthritis (about 70% of cases), and is
.,,
0
divided into 3 types (systemic, pauci- or oligoarticular and polyarticular). Systemic is
3
OJ
usually seen in children of under 5 years of age. Presenting features include a high
fever, a characteristic rash with patches of e1ythema, often appearing in the evening
r+
m and exacerbated by warmth, and lymphadenopathy, splenomegaly and pericarditis.
>< Arthritis or arthralgia may not be present initially, but may develop later in the course
OJ
3 of the disease.
c. 3. Measles
Measles is a highly communicable disease spread by droplets, and rem.ains one of the
commonest childhood infections in developing countries. The incubation period varies
from 8 to 14 days. There are tvrn distinct phases of illness: the pre-eruptive catarrhal
stage, followed by the exantheniatous stage. Initial symptoms include cough, c01yza and
conjunctivitis for 2-4 days, followed by fever and the appearance of a discrete, then a
confluent, red, maculopapular rash. It typically first appears behind the ears and then
sequentially on the face, neck, trunk, upper limbs, then buttocks and lower limbs. Koplik
spots (white spots on a red buccal mucosa) are found 1-2 days before the rash and last
3-5 days. Measles is infectious from 1 to 2 days before the onset of symptoms to 4 days
after the appearance of the rash. Cornplications include otitis n1edia, pneumonia and
encephalitis.
22
A 3-week-old baby is admitted with a 2-day history of poor feeding, fever and
vomiting. She has a temperature of 38.8 ° e, a 4 cm hepatomegaly, a full fontanelle,
reduced four limb tone, but normal tendon reflexes; she is jaundiced, floppy and
sleepy. Examination shows no rash and other systems are normal. Antenatal and initial
neonatal history is unremarkable, but feeding was difficult and her birthweight of
3100 g has not been regained. Initial investigations are as follows:
Haematology: Hb 13.2 g/dl, wee 22.7 x 109/1, Platelets 32 x 109/I, Prothrombin
time 23 s, APTT 78 s
Bioc�stry: Na 127 mmol/1, K 4.7 mmol/I, urea 6.8 mmol/I, creatinine 52 µmol/I,
CRP 198 mg/I, glucose 1.2 mmol/I, ALT 256 IU/I, albumin 28 g/I, bilirubin 249 µmol/I
(conjugated 26%), venous pH 7.26, bicarbonate 16 mmol/I, ammonia 52-mmol/l,
lactate 1.9 mmol/I
Microbiology: blood culture, no growth at 48 h. esF microscopy: Gram-negative
bacilli, polymorphs +++ (confirmed on culture), urine leucocytes ++, coliforms
>105 organisms/ml
Radiology: CXR normal
After the baby's hypoglycaemia has been corrected, she is started on i.v. cefotaxime
and ampicillin, and nasogastric tube feeds, but 8 days later there is little discernable
improvement. The repeat CSF culture is sterile, and although she has been apyrexial
since treatment day 4, she continues to be drowsy, jaundiced and to vomit. A CT brain
scan is normal. Further test results:
Haematology: Hb13.6 g/dl, WCC 12.7 109/I, Platelets 47 x 10 9/1, Prothrombin time
25 s, APTT 77 s
Biochemistry: Na 129 mmol/I, K 3.2 mmol/I, urea 7.1 mmol/I, creatinine 51 µmol/I,
CRP 65 mg/I, glucose 2.3 mmol/I, alanine aminotransferase 397 IU/I, albumin 25 g/I,
bilirubin 312 µmol/I (conjugated 26%)
Urine: sterile, Clinistix protein +, bilirubin +, pH 5, glucose -, Clinitest +
What is the most likely underlying diagnosis?
i. alpha-1-antitrypsin deficiency
ii. Galactosaemia
iv. Alagille syndrome
v. Pseudo-Bartter syndrome
vi. Neonatal amyloidosis
vii. Herpes simplex infection
viii. Wilson's disease
23
ii. Galactosaemia
Galactosaemia is the most likely diagnosis in this case and an assay of galactosc-l
phosphate uridyl transferase (Gal-l-P UT) should be requested to confirm_ it.
Management involves stopping milk feeds and starting a galactose-free formula. In a
neonate with a fever, a full septic screen is mandatory. Neonatal sepsis with Esclzcriclzia
coli should always prompt a consideration of galactosaemia as an underlying diagnosis.
Further clues in this case are acidosis; hypoglycaemia; the presence of hepatomegaly
with deranged liver function and coagulopathy; and acidic urine that contains reducing
substances other than glucose. The condition presents only once feeding has been
commenced and the lactose in breast or standard formula milk is metabolised to glucose
and galactose. The consequent accumulation of galactose-lphosphate (in the absence
of Gal-1-P UT) is injurious to the parenchymal cells of the liver, kidney and brain.
Clinistix tests only for the presence of glucose so a positive Clinitest but negative
Clinistix result indicates the presence of a reducing susbstance other than glucose
(galactose). Stopping milk feeds and starting a galactose-free formula usually results in
a dramatic improvement. Early diagnosis by Gal-l-P UT assay and dietary restriction
.,
0
of lactose intake do not prevent long-term complications, which include neuro
developn1ental problems, particularly -with language acquisition, and premature ovarian
3OJ failure ,vith infertility in females. The endogenous production of galactose n1ay be
ri-
m
responsible for these long-term effects. Follmv-up throughout life is mandatory.
><
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3
24
s::
;,::,
.,,
()
()
.,,
I
0)
;::i
N
Fig 1.12
An infant born at 33 weeks' gestation with a birthweight of 1596 g (3 rd-10th centile)

and a head circumference of 26.6 cm (3 rd centile), was, at delivery, in good condition,
but had bilateral arthrogryposis with fixed flexion deformities of arms, bilateral talipes
and fixed flexion of both hips. He made few spontaneous movements and at 6 h of
age generalized seizures began, which were difficult to control despite anticonvulsant
medication. An initial FBC showed:
Hb 13.8 g/dl
Total wee4.64 X 109/I
Neutrophil count 1.54 x 109/I
Lymphocytes 2.56 x 109/1
Nucleated red cell count 51 per 100 WBC
A cranial ultrasound scan was also performed which is shown in Figure 1.12.
i. Arthrogryposis multiplex congenita
ii. Infant of a drug-abusing mother
iii. GM1 gangliosidosis
iv. Congenital CMV infection
v. Congenital rubella infection
b. What investigations would you perform to confirm the diagnosis?
i. Serology for congenital infections
ii. CSF for CMV
iii. Urine toxicology
iv. Hearing test
v. Ophthalmology review
vi. Skull X-ray
vii. Genetic testing
c. What does the ultrasound scan show?
i. Arteriolar calcification
ii. Subependymal calcification
iii. Periventricular leukomalacia
iv. lntraventricular haemorrhages with dilatation
v. Periventricular parenchymal echodensities
25
ANSWERS CASE 1.12
a. iv. Congenital CMV infection
b. i. Serology for congenital infections
0
ii. CSF for CMV
to·
C:
v. Ophthalmology review
c. v. Periventricular parenchymal echodensities
:::J
Vl
OJ
The 1nost likely diagnosis is congenital CMV infection. To confirn1 the diagnosis, urine
:::J must be sent for CMV culture, and serology for congenital viral infections. PCR for
0..
CMV can be perforn1ed on urine, serun1 and CSF. Examination of the retina is irnpor
)>
:::J
VI
tant to look for evidence of chorioretinitis.
�
(t) The USS shows bilateral periventricular parenchymal echodensities, indicating areas of
""'I
VI
periventricular haemorrhage, infarction or possibly calcification. The lack of shadow
-+-,
0
""'I
behind the echodensities is against them being calcified lesions but this is better con
,-+ firmed with CT scanning. Maternal serology and serum PCR for congenital viral
:::;
(t) infections will help confirm the diagnosis. Serology can also be checked from booking
z
(t)
bloods.
�
.,,
0
Congenital CMV is the comrnonest cause of congenital infection with an estimated
frequency of 0.3-0.4% in the UK. However, over 90% of infants v.rith congenital CMV
3 are asymptorn.atic in the neonatal period, although many are growth retarded. Previous
OJ
,-+ infection is very common with 50% of women seropositive at booking. The risk of
m fetal infection depends on whether infection is primary or a re-activation. There is a
><
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25% risk of transplacental transrn.ission with prirn.ary infection and a 2% risk during
3 re-activation. However, because so ni.any w01nen are seropositive at conception, reac
tivation produces n1any more cases. The risk of sequelae also varies depending on
whether infection is prirnary or a re-activation. Most infants who are asyrn.ptomatic in
the neonatal period develop normally and have a normal IQ, and this _includes most
of those infected by re-activation. In one study following prirn.ary infection, 33% of
infants had sequelae; however, following re-activation, only 14% had sequelae, and
these tended to be less severe. Mortality from symptomatic neonatal CMV infection is
between 10 and 30%.
Important sequelae include sensorineural deafness, microcephaly, developn1ental delay
and cerebral palsy.
26
An 8-year-old boy from a travelling family presented to the emergency department
with a fever of 39.5 ° ( and a painful swollen right ankle. He had been coryzal over the
previous 3 days. There was a history of a fall 2 weeks previously but he had fully
recovered. There was no other significant past medical history. He did not receive any
of his childhood immunisations. The family is currently living on a site near a local
moor. On examination, there was no cardiovascular compromise. He had a coryza with
associated cervical lymphadenopathy. His right ankle was hot and swollen, and he
resisted any attempt to move it. Remaining examination wa-s unremarkable. The
following results were obtained:
Hameoglobin 9.4 g/dl
MCV 69.7 fl
WBC 20.9 x 109/I
Neutrophils 16.2 x 109/I
CRP 118 mg/di (normal range <10 mg/di)
The decision was made to start intravenous benzylpenicillin and flucloxacillin. As these
were being administered the nurse noticed a purpuric rash that had not been there
previously.
i. Meningococcal septic arthritis
ii. Henoch-Schonlein purpura
iii. Von Willebrands disease with intraarticular haematoma
iv. Lyme disease
v. Disseminated intravascular coagulation
vi. Parvovirus B19 infection
27
ANSWER TO CASE 1.13
i. Meningococcal septic arthritis
D The specific treatment is high-dose intravenous third-generation cephalosporin anti
C:
biotics. Supportive treatment is critical to survival in n1eningococcal septicaemia, and
� these children often require invasive monitoring and treatment in intensive care.
a· Contact tracing with appropriate antibiotic prophylaxis and immunisation of at-risk
::J
I.fl
OJ
individuals in the immediate community is normally pe1forn1ed by public health physi
::J cians. Definitive diagnosis in suspected septic arthritis is made following analysis of
0..
aspirate frorn the affected joint. Pe1formed under surgical conditions, this also gives the
)>
::J opportunity to wash out the joint and im1nobilise in a functional position. The co
existence of arthritis and a purpuric rash is classically seen in Henoch-Schonlein purpura
CD
'""'I
I.fl
(HSP) which is the n1ost common of the vasculitides affecting children. Septic arthritis
-+, with DIC should be considered. The most common organisms isolated in septic arthritis
0
'""'I are Staphylococws aureus, Streptococws pneumoniae and Salmonella sp., and in the unin1-
,-+
-::::r munised child Haemophilus iiif/uenzae b and Neisseria meningitidis are well recognised but
CD
rare causes. Mycobacteria may also cause septic arthritis but this is less commonly
z
CD associated with DIC. Lyme disease (Borrelia burgdo,jen) is frequently associated with an
arthropathy. It is caused by the bacteriun1 carried by ticks in endemic areas (often open
"Tl
0 moorland in the UK).There is usually a history of flu-like symptorns, and patients n1ay
3
OJ
have a rash with purpuric elements, although this usually evolves fr01n the classic rash
,-+ of erythen1a migrans. Both purpura and arthritis are recognized as m.anifestations of
m Parvovirus B 19 infection or Fifth disease, although the laboratory results in this case
><
OJ are more in keeping with a bacterial aetiology.
3
28
A 12-year-old West Indian boy presented with symmetrical swelling of his fingers. One
week previously, he had complained of a severe sore throat and had developed a s;:
papular rash after having been prescribed amoxicillin. The hand swelling had developed ::;o
n
gradually during the day of presentation. On examination, he was afebrile. There was "'O
n
widespread lymphadenopathy and mild pharyngitis. There was left upper quadrant I
tenderness and his spleen was palpable 3 cm below the costal margin. On examination "'O
OJ
of both hands he complained of pain over the metacarpophalangeal and phalangeal �
joints. Both ankles were swollen. He had restricted movement in all affected joints. N

i. Coxsackie infection
ii. Epstein-Barr virus infection
iii. Lyme disease
iv. Thalassaemia
v. Sickle cell syndrome
vi. Post-streptococcal arthritis
vii. Juvenile idiopathic arthritis
29
ANSWER TO CASIE 1.14
ii. EBV infection
,0 The most likely diagnosis is EBV infection. The physical findings are consistent with
C
this diagnosis. Arthritis and arthralgias are common in many viral infections. Joint
�
Cl)
a·
::J
lesions are due to the deposition of immune complexes and not direct viral infection.
The arthritis is usually transient and self-limiting. The prodrome in this case included
VI
0,
a papular rash following amoxicillin as classically seen in EBV. Investigations should
:::i include blood filrn, Hb electrophoresis, viral serology, complement, and streptococcal
0..
serology. A blood film may be diagnostic in a sickle cell crisis. It may also show char
)>
::J
VI
acteristic lymphocyte morphology in EBV infection. Hb electrophoresis will diagnose
:;E sickle cell disease. A request for viral serology should include EBV, hepatitis A and B,
Cl)
""'I
VI
CMV, coxsackie, echovirus and adenovirus. A stool sample for virology may increase
-+. the chances of viral identification. Rubella should be considered in unimmunised
0
""'I individuals. Con1plen1ent C3 and C4 will be reduced in systemic lupus erythematosus
,-+
::::; as well as post-streptococcal arthritis. An elevated or rising ASOT titre indicates recent
Cl)
streptococcal infection but may take a week or 1T10re to rise.
z
ro
:;E Positive serology confirn1ed EBV infection. Dactylitis is frequently the presenting
.,,
0
complaint in sickle cell disease ,vhich must be excluded in a boy of West Indian origin .
3
0,
Post-streptococcal arthritis may exist as a distinct disease entity or be part of rheumatic
fever. JIA and syste1nic lupus erythematosus need to be considered as part of the initial
,-+
m differential diagnosis.
><
0,
30
An infant born at 28 weeks' gestation suddenly collapses at 3 weeks of age. She was
initially ventilated for 10 days and has since been stable on NCPAP in 26% 0 2 . She is
currently receiving total parenteral nutrition via a percutaneous long line situated in the
right atrium and is on 4 ml/h of enteral feed via a nasogastric tube. At the time of
collapse, she is poorly perfused with a capillary refill time of 6 s, is tachycardic at 195/
min, and has a blood pressure of 36/28 mmHg. There is no heart murmur but heart
sounds are quiet. An arterial gas reveals a mixed respiratory and metabolic acidosis.
Following ventilation and stabilisation, a CXR shows a massively enlarged cardiac
shadow with normal lung fields. Her cranial ultrasound shows bilateral grade 1
intraventricular haemorrhage.
i. Cardiac tamponade
ii. Tension pneumothorax
iii. Overwhelming sepsis
v. Increased intracranial pressure
vi. An inborn error of metabolism
31
ANSWER TO CASE 1.15
i. Cardiac tamponade
D Differential diagnosis should include cardiac tamponade, septicaemia, congenital heart

C
<D disease, or an inborn error of n1etabolisn1. Echocardiography is the investigation of
!!]. choice, which will not only confirm a pericardial effusion, but also exclude congenital
o·
:::,
heart disease.
V'l
0) Cardiac tan1ponade in this case has occurred secondary to a long line which has
:::,
a. migrated into the pericardial sac. Percutaneous long lines should be positioned just
)> outside the heart either in the superior or inferior vena cava. It is vital that the tip is
:::,
clearly visualised. If it is placed in the right atrium, it must be withdrawn and re-X
�
<D rayed. If the tip cannot be seen, contrast n1edium should be used.
"""I
V'l
-+, Management involves ren1oval of the long line and drainage of the pericardial effusion
0
"""I using the subxiphisternal approach. After cleaning the skin, a 22/24 G cannula should
,-+
::, be inserted at an angle of 30 ° to the skin, directed towards the left shoulder. Aspirated
<D
fluid should be sent for microbiological and biochemical assay. Only if the effusion
z
<D reaccumulates will it be necessary to leave a catheter in situ. In this case, the drained
�
,,
0
fluid vns confirmed to be TPN.
3
OJ
,-+
m
><
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32
Fig 1.16.A
Fig 1.16.B
Following induction of labour at 41 weeks' gestation for maternal byR_e_ili'J1$ion, an
infant (birth weight 3000 g) wa�_delivered normally and cried immediately, requiring no
resuscitation. At approximatel(�_b)of age, after transfer to the post-natal ward with
her mother, she was admitted to the neonatal unit because of tachypnoea, poor
feeding and jitteriness. The blood glucose, electrolytes and serum creatinine were
normal. A septic screen was performed and she was commenced on i.v. antibiotics. A
blood gas on admission to the neonatal unit showed:
pH 7.323
pCO2 2.81 kPa
Bicarbonate 11.2 mmol/I
Base excess -11.9 mmol/I
Lactate 7.50 mmol/I (<2 mmol/I)
Other investigations showed:
CSF clear/colourless with no organisms or white blood cells
Glucose 3.5 mmol/I
Lactate 16.2 mmol/1.
The results of an MRI brain scan are shown above.
a. What do the results indicate?
i. Compensated respiratory acidosis
ii. Metabolic acidosis
iii. Mixed metabolic and respiratory acidosis
iv. Compensated metabolic acidosis
v. Respiratory alkalosis
What other investigations are necessary?
i. Skin biopsy
ii. Urine amino acids
iii. DNA analysis
iv. Plasma ammonia
v. Serum organic acids
vi. Electroencephalogram
What is the differential diagnosis?
i. Methylmalonicacidaemia
ii. Glycogen storage disease type 1
iii. Organic acid disorders
iv. Urea cycle disorders
v. Pyruvate dehydrogenase deficiency
vi. Non-ketotic hyperglycinaemia 33
ANSWERS TO CASIE 1.16
a. iv. Compensated metabolic acidosis
b. i. Skin biopsy
D ii. Urine amino acids
C:
� iv. Plasma ammonia

o· c. ii. Glycogen storage disease type 1
::::,
VI iii. Organic acid disorders
O.>
::::,
v. Pyruvate dehydrogenase deficiency
a.
The results show a primary lactic acidosis with a cerebral lactic acidosis. She is blowing
)>
::::, off her CO 2 to compensate for the acidosis.
(D The MRI scan shows dilated lateral ventricles and a thin corpus callosum. Investigations
"""I
VI should include urinary amino and organic acids, serun1 amino acids and plasn1a a1ru11onia.
Skin biopsy may be helpful for fibroblast culture and specific cytogenetic analysis. Dif
,-+ ferential diagnosis of primary lactic acidosis includes glycogen storage disease type I,
::::;
(D organic acid disorders, disorders of pyruvate metabolism, disorders of gluconeogenesis
z and electron transport chain defects.
(D
This infant presented with non-specific features but the initial blood gas found a severe
-r,
0 lactic acidosis. There was no evidence of an earlier hypoxic ischaemic insult therefore
3 a lactic acidosis secondary to a hypoxic event was extremely unlikely. The MRI scan
OJ
,-+ suggests an early antenatal insult and these changes are common in infants with prirn.ary
m lactic acidosis. Lactic acidosis presents a difficult diagnostic problem as prirn.ary lactic
X
OJ
acidosis produces many of the circulatory problems which cause secondary lactic aci
3 dosis. It is important in this situation to seek the advice of a biochemist or clinician
with expertise in metabolic diseases, as investigation and therapy can be difficult. Some
conditions require treatrn.ent with carbohydrate supplementation and others are made
worse by this regirnen. This infant had pyruvate dehydrogenase deficiency which has
an incidence of 1 in 200 000 and is usually inherited as an X-linked dominant condi
tion. It typically presents with severe acidosis or profound neurological deficit and
structural brain lesions. It is usually caused by deficiency of the Ela-subunit which is
on the short arm of the X chrornosome. Both hemizygous males and heterozygous
fem.ales are affected, nearly all cases being due to new nmtations. Patients with structural
brain lesions are usually fem.ales with severe enzyme lesions which destroy patches of
the brain in which the mutant gene is active. Males usually present with early severe
acidosis.
34
A 3-year-old boy is admitted to hospital following two episodes of abnormal
movements. His mother reported that on two consecutive mornings, whilst having his
breakfast, the right side of his face and his right hand were twitching for about 30 s.
s:
;::o
{')
He appeared to be conscious throughout both episodes. Afterwards, he recovered '"O
{')
completely, although following the second episode he fell asleep on the sofa. His twin I
brother used to have uncomplicated febrile convulsions in the past. He and his brother '"O
OJ
were adopted at birth. Growth parameters are all on the 50th centile. Clinical ;::i
examination including fundoscopy was entirely normal. EEG showed left-sided N
centrotemporal spikes.
i. Temporal lobe epilepsy
ii. Hypnagogic myoclonic seizures
iii. Febrile convulsion
iv. Simple partial seizures
v. Benign Rolandic epilepsy
vi. Complex partial seizures
35
CASIE 1.17
v. Benign Rolandic epilepsy
In all cases of seizures, a detailed developmental hist01y should be taken. The family
hist01y should also be taken, although this is more difficult in this case since the child
was adopted.
Differential diagnosis fron1 the history and examination includes benign Rolandic epi
lepsy of childhood or sin1ple partial seizures. The EEG here showed left-sided centro
tem_poral spikes, which is typical for benign Rolandic epilepsy of childhood and can
also be bilateral. A sleep EEG often intensifies the spike activity. Further investigations
like neuro-imaging are not indicated because of the diagnostic nature of the EEG and
the absence of any neurological abnormalities on clinical examination.
The best treatment for benign Rolandic epilepsy is not to treat! The condition is benign
and because the seizures usually occur during sleep or on waking, it is well tolerated.
If the seizures are interfering with schooling or quality of life, carbamazepine or val
proate may be used. The age of onset is bet,veen 3 and 13 years. Prognosis is excellent.
Seizures commonly stop at the age of 12 years and the EEG normalizes several years
,,
0
later. There is no increased risk of seizure development in later life. This is a genetic
disorder transmitted as an autoson1al dominant trait. Forty percent of close relatives
3
OJ
have a hist01y of febrile convulsions or epilepsy.
r+
m
><
OJ
3
36
An 8-month-old infant has frequent episodes of hypoxia post-operatively following
uncomplicated bilateral inguinal herniotomies. He is now 12 h post-operation and his
oxygen saturation is 88% in air. He has required bag and mask ventilation on a couple
of occasions for apparent apnoeas. On examination, he is extremely pale and
tachycardic with a heart rate of 190/min. His heart sounds are normal, but he has a
gallop rhythm. He is tachypnoeic with a respiratory rate of 60/min and has mild
intercostal recession, but his chest is entirely clear. He has a palpable liver 2 cm below
the costal margin. He has bilateral haematomas at the incision sites. He is well grown
for his age, but his mother mentions that he always looks a bit pale. His post-operative
Hb is 4 g/dl and his platelet count is 224 x 109/L. His activated partial thromboplastin
time was very prolonged with a normal thrombin and prothrombin time.
What is the likely underlying condition?
i. Bernard-Soulier syndrome
ii. Antithrombin Ill deficiency
iii. Cardiomyopathy
iv. Vitamin K deficiency
v. Haemophilia A
vI. Von Willebrand's disease
37
ANSWER TO 1.18
v. Haemophilia A
t:) The most likely diagnosis here is haemophilia A (although haen1ophilia B cannot be
C
excluded).
�
11)
o· This little boy had developed heart failure secondary to anaen1ia. Because of the exten
:::,
V'I sive haematomas, it is important to ask whether he has a histmy of easy bruising and
0) nose bleeds and if there is a family histo1y of bleeding disorders. Particular attention
:::,
a.. should be paid to any histmy of prolonged bleeding following sin1ple procedures such
)> as circumcision and childbirth.
:::,
V'I
:§: Investigations should include a repeat FBC and film, coagulation profile and CXR.
11)
--;
V'I
The blood film ,vill look at red blood cell morphology. In this patient, the anaemia
--+, was normocytic. A preoperative Hb had not been done. A clotting profile is warranted
0
--; in any patient with unexplained/disproportionate bruising, particularly if rnale. His
,-+
:, activated partial thromboplastin tirne was ve1y prolonged with a norrnal thrombin and
(I)
prothrombin time. A CXR will exclude causes for his respirato1y deterioration other
z
11) than heart failure. This patient did have haemophilia A as confirn1ed by measuring his
:§:
,,
0
clotting factors. He had a very low level of factor VIII (2.5%). A level of <1% is con
sistent with severe haen10philia and usually presents with easy bruising in infancy. They
3
Q)
do not bleed excessively from_ cuts or from_ nrncosal surfaces unless raw areas exist.
,-+
m Treat1nent involves a blood transfusion and an injection of factor VIII concentrate.
>< The circulating level was raised by 30%, which usually achieves haemostasis, using
Q)
3 15 units/kg of factor VIII.

Haemophilia A is inherited as an X-linked recessive condition and parents need genetic
counselling for future pregnancies.
38
A term baby boy was admitted to the neonatal unit at 4 h of age with grunting and
respiratory distress. On admission he was noted to be micrognathic, with a cleft palate,
syndactyly of the 2nd and 3rd toes of both feet and mildly reduced tone.
s:::p
(')
'"tJ
a. What is the most likely cause of his respiratory distress? (')
SELECT ONE ANSWER ONLY '"tJ
i. Respiratory distress syndrome 0,
;:i
ii. Sepsis N
iii. Micrognathia
v. Hypotonia
b. What would your initial management be?
SELECT THE TWO MOST APPROPRIATE ANSWERS
i. Nasopharyngeal airway care
ii. Place him supine
iii. CPAP
iv. Intubate and ventilate
v. Septic screen and treat empirically with antibiotics
Progress was slow and he remained reluctant to feed, requiring top-ups via a naso
gastric tube to ensure adequate calorie intake. At 4 weeks of age he developed
persistent vomiting. A repeat septic screen was performed. The venous blood gas
revealed a pH of 7.49, bicarbonate .of 36.2 mmol/1 and potassium of 3.0 mmol/1.
'} _;,,.':e,
i
c. What syndrome is he most likely to have?

i. Holt-Oram
ii. Pierre-Robin
iii. Smith-Lemli-Opitz
iv. Ellis-Van Creveld
v. Rubinstein-Taybi
39
ANSWERS TO CASE 1.19
a. iii. Micrognathia
b. i. Nasopharygeal airway
D v. Septic screen and treat empirically with antbiotics
C
�
(I) c. iii. Smith-Lemli-Opitz
o·
::J His respiratory distress is secondary to his micrognathia and cleft palate (the Pierre
Vl
Robin syndrome), causing soft-tissue obstruction of his ainvay by his posteriorly placed
Q)
::J tongue. His hypotonia \Nill contribute to worsen this effect. Sepsis as a cause for
0.
respiratory distress must be considered in all neonates irrespective of gestation and this
)>
::J may coincide with structural abnormalities.
� Managen1ent of his respiratory distress involves the following: a prone position, a
�
nasopha1yngeal airway to help with breathing, and a maxillofacial team and speech
-
0
..., therapy opinion regarding the fitting of a plate over the cleft to aid feeding and feeding
,-+ advice. A septic screen including CXR should be considered in all umvell neonates.
::::,
(I)
This baby developed hypertrophic pyloric stenosis (obstruction to the outflow tract of
z
(D the stomach seconda1y to muscle hypertrophy). A test feed can be pe1formed to
,,
0
confirm this diagnosis, palpating an olive-shaped mass in the right hypochondriurn. If
the test feed is equivocal then an ultrasound scan is helpful.
3
Q) This baby was subsequently diagnosed as having S1nith-Lemli-Opitz syndrome, a
,-+
m
disorder of cholesterol synthesis which is associated with an increased rate of pyloric
>< stenosis. The main features of this syndrome are developmental delay, poor growth,
Q)
3 cleft palate, genital anomalies and syndactyly or polydactyly.
40
Right Left
FREQUENCY - Hz FREQUENCY - Hz
�
.,,
:::0
n
10 10 n
.,,
I
20 20
30
40 ...
,_.
) !i:.
30
40 ..... . ll>
50
60
70
.�
-... "'�""
,.,
�I,_/ 50
60
70
'"' �
N
80 80
90 90
100 100
110 110
120 120
250 500 1000 2000 4000 8000 250 500 1000 2000 4000 8000
3kHz 6kHz ....... 3_kliz_ .. _6k� ....
Tympanogram: BONE CONDUCTION
� L y,:_ vz_ Masked right [ Masked left ]
Fig 1.20
What does this pure tone audiogram show and what might cause this picture?
SELECT THE BEST PAIR OF ANSWERS
A. Right conductive hearing loss 1. Pendred syndrome
B. Bilateral moderate conductive hearing 2. Intrauterine group B strep infection
loss 3. Recurrent secretory otitis media
C. Bilateral mixed conductive and sensori 4. Neonatal conjugated
neural hearing loss hyperbilirubinaemia
D. Within normal limits 5. Upper respiratory tract infection
E. Bilateral moderate sensori-neural 6. Bilateral perforated ear drums
hearing loss 7. Bilateral cleft palate
F. Right sensorineural hearing loss
G. Bilateral high-frequency sensori-neural
hearing loss
41
ANSWER TO CASE 1.20
E.and1.
(Bilateral moderate sensori-neural hearing loss and Pendred syndrome)
Subjects with normal hearing can hear pure tones 20 dB (decibel hearing loss) or less.
The air conduction thresholds in the right ear (circle) show a hearing level of 60 dB
at 500 Hz-1000 Hz, rising to 40 dB at 4000 Hz. On the left (cross) the range is 50-
55 dB. There is equal impairment of air and bone conduction in sensorineural hearing
loss. In conductive hearing loss there is a difference of at least 15 dB between air and
bone conduction ('air-bone gap').
Causes of sensori-neural hearing loss may be congenital or acquired.
Congenital causes of sensori-neural hearing loss

Isolated sensorineural hearing loss is the conunonest cause of sensori-neural deafoess
r-+ (inheritance autosomal recessive but autosomal dmninant and sex-linked transmission
::::;
Cl) also occurs). Severe (65-80 dB) and profound (85 dB) sensorineural loss affects 1 in
z
Cl)
1000 children, but the incidence can be as high as 1 in 40 in very low birth weight,
ventilated babies.
.,,
0 Syndromes with deafness are much less common, and include:
3 Chromosomal, e.g. Turner's syndrome
OJ
r-+ • Ophthalmological, e.g. Usher's (with progressive retinitis pigmentosa and cataracts)
m • Ectodermal/pigmentary, e.g. Waardenburg's (autosomal dominant, dysmorphic fea
><
OJ
tures such as broad nasal root, hyperplasia of medial aspect of eyebrows, white or
3 grey lock of hair or early greying, heterochromia of irises)
Skeletal/craniofacial, e.g. Treacher-Collins (autosomal dominant, hypoplasia of
mandible, high-arched or cleft palate, oblique palpebral fissures, microtia with absent
external auditory canal). Goldenhar's syndrome also features ear abnormalities with
deafness, and vertebral anomalies, eye defects (coloboma, cataracts or epibulbar
dermoids) and characteristic facies of frontal bossing, small mandible and nostrils.
Metabolic/endocrine/renal, e.g. Pendred syndrome (hypothyroidism_), Alports (renal),
Jervell-Nielson (prolonged QT interval).
Acquired causes of sensorineural deafness

• Intrauterine infection (CMV, rubella, toxoplasmosis, syphilis)
• Perinatal asphyxia
o Neonatal hyperbilirubinaemia
• Infections, e.g. bacterial meningitis (pneumococcus, H. injluenzae, and rneningococcus)
Drugs, e.g. aminoglycosides
42
r
Fig 2.1
A 13-week-old baby girl is referred to the outpatient department for a prominent and
protruding forehead. According to her mother this has always been the case though to
a lesser extent than when she was born. The child is otherwise well, weight following
the 0.4th centile, length along the 9 th centile and head circumference on the 50th
centile. The parents are not concerned about the head shape but the child's GP is and
hence the referral.
On examination the child appears well. She has a very small anterior fontanelle and
frontal prominence.
What do the skull X-rays show?
i. Wormian bones
ii. Ridging of sutures
iii. Fused sagittal suture
iv. Fused lamboid suture
v. Dolicocephalic head shape
vi. Fused coronal suture
45
ANSWERS TO CASE 2.1
iii. Fused sagittal suture
v. Dolicocephalic head shape
,0
C:
l'D Both X-ray views show a fused sagittal suture throughout its length. The dolicocephalic
�
,s- head shape is seen in Figure 2.1.1.
::::i
Vl The diagnosis here is sagittal craniosynostosis. Other features to look at in the examina
0, tion include head shape, e.g. long and narrow dolicocephalic, short and square -
:::J
0.. brachycephalic; ridging of sutures; and fingers and toes should be examined for
)> abnornialities.
::J
Treatn1ent involves urgent referral to a designated centre for craniofaciaJ surgical assess
l'D
"""I
Vl
ment. A nrnltidisciplinary team_ con1prising the neurosurgeon, plastic surgeon and
-+, neurologist manage the condition.
0
"""I
r+ Craniosynostosis occurs when there is lack of dural gr0vvth from restricted cranial
:J"
l'D expansion or limited brain growth. The 1nost conu11on cause of isolated craniosynostosis
z
l'D
is constraint of the fetal head. The incidence of this problem is about 1 in 1000
births.
"TI
0 Sagittal craniosynostosis is the most common type, with a 3 : 1 predilection for males,
3OJ due to more rapid head growth in males during late gestation. The head shape is
r+ dolicocephalic. Coronal craniosynostosis may occur by itself, or as part of an autosomal
m
><
dominant disorder such as Crouzon syndrome, Apert syndrome, Pfeiffer syndrome, or
OJ Saethre-Chotzen syndrome, in which various types of limb abnormalities may be
3 present. Lambdoid craniosynostosis accounts for less than 3% of all cases.
The designated centres for craniosynostosis treatment in the UK are 111 Oxford,
Birmingham, and Great Ormond Street.
46
A male infant was born at 31 weeks by caesarean section for reduced fetal movements
and being small for gestational age. He developed severe respiratory distress requiring
intermittent ventilation for 2 months. At birth, he was noted to have a spreading
s:
:::0
(')
petechial rash. He then developed a persistent conjugated hyperbilirubinaemia. He also -0
(')
had grade 3 intraventricular haemorrhage, dilated ventricles and intracranial I
parenchymal calcification. He developed grade 3 retinopathy of prematurity and -0
OJ
bilateral chorioretinitis. CMV PCR was highly positive, and blood cultures were negative. �
The infant received a 3 month course of ganciclovir, with a fall in his PCR value. He N
currently has hepatosplenomegaly and microcephaly with global developmental delay.
a. What could be the causes of the severe respiratory distress?
i. HIE
ii. CCAML
iii. Central hypoventilation syndrome
iv. CMV pneumonitis
v. Surfactant deficient lung disease
vi. Bilateral pleural effusions
b. What could be the cause of the hyperbilirubinaemia?
SELECT THE MOST APPROPRIATE ANSWER
i. Total parenteral nutrition
ii. lntrahepatic calcification
iii. CMV hepatitis
iv. Haemolysis
v. Physiological jaundice
47
ANSWERS TO CASE 2.2
a. iv. CMV pneumonitis
v. Surfactant deficient lung disease
,0
C b. iii. CMV hepatitis
�
(I)
Congenital CMV infection affects approximately l% of newborn infants, although n1ost

o·
:J
are asymptomatic. CMV is a herpes virus. It can be transmitted in utero (with a vertical
VI
ru
transmission rate of 40%), perinatally from infected cervical secretions or postnatally,
:J acquired fron1 breast milk or through blood transfusion. CMV is excreted in saliva,
Q..
urine, semen, cervical secretions, stool and tears. Approximately 90% of infants
)>
:J are clinically asymptomatic and have a favourable outcome, although they are at risk
(5-l7%) of developing sensorineural hearing loss, chorioretinitis, learning difficulty and
(I)
VI
neurological deficits. About l0% exhibit a wide variety of signs and symptoms such as
-+, intrauterine growth retardation, jaundice, hepatosplenomegaly, petechiae or purpura,
0
..., thrombocytopenia, pneumonia, chorioretinitis (l0-20% of symptomatic infants), intra
,-+
::::; cranial calcification (often periventricular, affecting 25-50% of symptomatic infants),
(I)
sensorineural hearing loss (50%), seizures and microcephaly. Of those infants who are
z
(I) asymptomatic, 90% have long-term sequelae such as sensorineural hearing loss (usually
in first 3 years of life), motor and intellectual disability, seizures and chorioretinitis.
"Tl
0
3
ru
The diagnosis is made by viral culture of the urine, blood, CSF or nasopharynx (in
first 3 weeks of life). Other tests include enzyme linked immunosorbent assay (for
,-+
m CMV) specific IgM, or PCR.
X
ru
Ganciclovir is currently being investigated for use in infants ,vith symptomatic con
3 genital infection and CNS disease. Anecdotal evidence suggests that critically ill new
borns with CMV pneumonia may benefit from this drug.
48
A 10-year-old boy presented with his first afebrile convulsion. His parents describe a
5-minute generalised tonic-clonic convulsion, from which he fully recovered 90 min �
later. He is developmentally normal, with no previous medical history of note. He has ;o
n
become upset recently over his continued bed-wetting, and his GP recently prescribed a -0
n
'night-time tablet', his parents say, to help. Since starting he has been dry at night. ::c
-0
a. What is the likely cause of the fit? OJ
;:l.
SELECT ONE ANSWER ONLY N
i. Pseudoseizures
ii. Dehydration
iii. Epilepsy
iv. Hyponatraemia
v. Benign Rolandic seizures
vi. Hypernatraemia
b. What investigation should be done first?
i. Serum electrolytes
ii. Water deprivation test
iii. EEG
iv. Lumbar puncture
V. ECG
c. What is the treatment?
i. i.v. fluid bolus of 0.9% saline
ii. Stop the medication
iii. Restriction of his fluid intake
iv. Sodium valproate
v. Carbamazepine
vi. No treatment necessary
49
a. iv. Hyponatraemia
b. i. Serum electrolytes
D
C c. ii. Stop the medication
(I) iii. Restriction of fluid intake
�
5· This seizure is secondary to hyponatraemia with ,,vater overload, secondary to rnedica
:::::i
VI
OJ
tion. He had been prescribed 'desmotabs' (vasopressin) 3 weeks earlier to control his
:::::i enuresis. The risk is from ,,vater overload, and the information sheet provided ,vith
a.
desmotabs, stresses the importance of avoiding excessive evening drinking. As with any
)>
:::::i n1edicine, there is always a risk of overdose, intentional or accidental.
(I) It is in1perative to measure serum electrolytes, which would demonstrate low sodium.
""'I
VI Water restriction is usually sufficient to correct hyponatraemia if the cause is water
-+,
0
""'I
overload, especially in this case when the source of the water overload is removed (i.e.
,-+ stop the medication). Regular checking of the serum electrolytes confirms the nor
::;
(I) malisation of the sodium.
z
(I) Rarely hyponatraemia nmst be treated more rapidly, i.e. if the patient continues to fit.
.,,
0
In this case, ,;,,rhere there is water overload, infusing a small volume of hypertonic saline
helps shift fluid from the intracellular to the vascular space, and the extra water is
3
OJ
excreted by the kidneys.
,-+
m
><
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50
A 3-week-old boy was admitted with pyrexia, irritability, poor feeding and a high
pitched cry. He had been born by spontaneous vaginal delivery at 41 weeks' gestation,
weighing 3600 g. On examination his temperature was 38.8°e, there were two small
pustules on his chest; he disliked any handling and showed neck retraction. He was
tachycardic but well perfused.
Investigation results included:
esF microscopy:
RBe 220/mm3
wee 80/mm3 (90% lymphocytes)
No organisms
esF glucose 3.2 mmol/1
esF protein 1 .2 g/1
Blood glucose 4.4 mmol/1
6 h after admission, he started to have focal, right-sided seizures.
i. Staphylococcal scalded skin syndrome
ii. Impetigo
iii. Tuberculous meningitis
iv. Herpes encephalitis
v. Meningococcal meningitis
vi. Non-accidental injury
What treatment should be commenced?
i. i.v. fluid bolus
ii. i.v. antibiotics and acyclovir
iii. i.v. mannitol
iv. Steroids
v. Anticonvulsants
51
ANSWERS TO CASE 2.4
a. iv. Herpes encephalitis
b. ii. i.v. antibiotics and acyclovir
,0
C v. Anticonvulsants
!!l
(I)
o·
:::l
Diagnoses of viral encephalitis, bacterial meningitis and sepsis elsewhere should all be
considered. A full septic screen should be pe1formed.
V\
0, Treatment should include acyclovir and antibiotics, and anticonvulsants for seizure
:::l
0. control. The CSF findings are 111ore suggestive of viral infection but antibiotics should
)> be continued until cultures are negative. The vesicle fluid can be examined by electron
:::l
V\ microscopy for herpes virus particles.
.,
(I)
V\
Neonatal herpes simplex infection may occur in disseminated form, localized (skin, eye,
-h n1outh), or -with an encephalitis. It is usually caused by HSV type 2. In 50% of cases
.,
0
of herpes simplex encephalitis no vesicles appear. Neonatal herpes encephalitis has a
rl
:::; n1ortality of 151¾1 and a high risk of long-term_ neurological sequelae (>50%).
(I)
z
(I)
�
.,,
0
3
0,
ri-
m
><
0,
52
A term male infant was admitted to the neonatal intensive care unit at 12 h of age
because he was cyanosed. His apgar scores were 9 at 1 min and 9 at 5 min. He had
fed well though the midwife had felt he had never been pink.
s:
::x,
("I
iJ
His oxygen saturation was 68% in air and 70% in 3 I of oxygen via nasal prongs. The ("I
I
saturation remained low despite increasing supplemental oxygen and he developed
iJ
increasing respiratory distress. On examination his respiratory rate was 64 breaths/min OJ
;:::i
and heart rate 180 bpm. Chest examination revealed clear lung fields. He had an easily
N
palpable cardiac pulsation, normal peripheral pulses, normal heart sounds and no
audible murmur. The rest of the examination was unremarkable. His CXR showed a
slightly large heart with normal lung fields.
i. Transposition of the great arteries
ii. Tricuspid atresia with VSD
iii. Truncus arteriosus
iv. Total anomalous pulmonary venous drainage
v. Pulmonary atresia
vi. Fallot's tetralogy
An intravenous treatment was commenced on the baby.
b. What are the complications of this treatment?
i. Seizures
ii. Hypokalaemia
iii. Apnoea
iv. Hypertension
v. Hypotension
vi. Arrhthymias
vii. Haemorrhage
viii. Hyperkalaemia
53
TO CASE 2.5
a. i. Transposition of the great arteries
b. ii. Hypokalaemia
iii. Apnoea
v. Hypotension
Transposition of the great arteries is the most con1mon cyanotic congenital heart disease
OJ
(CCHD) accounting for approximately 5% of all congenital heart disease. It often co
::J exists with other cardiac defects, e.g. VSD that allow for better mixing of blood.
C.
)> The closing of the ductus arteriosus results in loss of mixing if there is no or only a
::J
sn1.all VSD, so it is crucial to conm1.ence an infusion of prostaglandin as quickly as
(D possible, to maintain patency of the ductus arteriosus.
"""I
II'
-+, However, this treatment is not without problems, so, ,;,,rhere possible, should be admin
0
"""I istered in an intensive care setting. Apnoeas can lead to the baby requiring ventilation,
r+
:::, especially if transfer to a specialist cardiac centre is needed. Other side-effects of pros
(D
taglandin include fever, flushing, hypotension and hypokalaemia.
z
(D
Definitive treatment for transposition is changing. Until the mid-1990s, a balloon atrial
,,
0
septostomy vvas pe1formed early on; then a permanent procedure was carried out at
3
OJ
6-9 months (Mustard or Senning operations). Now many centres maintain the duct by
the prostaglandin infusion and a definitive repair (arterial switch) is carried out within
r+
m
the first few days of life.
><
OJ
3
54
s:
;,:,
(')
'"O
(')
I
'"O
0,
;::i.
N
Fig 2.6.A Fig 2.6.B
An 8-year-old, previously healthy boy, presented with a 6 h history of fever, irritability

and drowsiness. On admission he was febrile, and had a widespread petechial rash. A
diagnosis of meningococcal septicaemia was suspected. Blood cultures were taken, and
he was commenced on intravenous antibiotics and resuscitated with 4.5% human
albumin solution. He deteriorated and was transferred to ITU where he was ventilated.
He required infusions of dobutamine, adrenaline and noradrenaline to maintain his
blood pressure, and he developed severe adult respiratory distress syndrome. He then
developed acute tubular necrosis and was haemofiltered. He had numerous vasculitic
lesions on his skin. Other complications were a pneumothorax, pneumomediastinum
and pulmonary haemorrhage. Both hips were normal at the onset of his illness. His
length of stay on ITU was 6 weeks but eventually he appeared to make a full recovery.
At outpatient review 4 months later, he complained of pain on walking and back pain,
and had limited abduction of both hips. His plain X-ray and bone scan are shown.
What is the most likely cause of his symptoms?
i. Osteoporosis
ii. Avascular necrosis
iii. Renal osteodystrophy
iv. Cerebrovascular event
v. Systemic lupus erythematosus
vi. Systemic juvenile arthritis
55
ANSWER TO CASE 2.6
ii. Avascular necrosis
D The plain X-ray shmvs severe flattening and sclerosis of both femoral heads. The bone
C scan shows reduced uptake of the tracer indicating avascular necrosis of both hips.
(I)
� Sequelae of meningococcal n1eningitis are conunonly neurological, notably deafoess.
o·
:::l
Complications arising from meningococcal septicaemia include the problems of the
VI
OJ vasculitic skin lesions and gangrene. Bony lesions are less commonly described. The
:::::i most likely aetiology of the avascular necrosis in this case is ischaemia either secondary
Q..
to en1bolism or hypoperfusion. The presence of bilateral fen10ral intravenous and intra
)>
:::i
VI
arterial lines n1ay have contributed towards the vascular compromise. It is possible that
,vith more aggressive therapy and improved survival v.rith severe meningococcal septi
ro
..... caemia, long-terrn complications such as avascular n_ecrosis will become n1ore evident
VI
-+, necessitating long-term follovv-up.
0
.....
r+
:::J"
ro
z
ro
�.,,
0
3
OJ
r+
m
><
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3
56
A 1-year-old child was referred by her GP to the community paediatric team, the main
parental concern being delayed motor milestones. The child was unable to sit or s::
weight-bear, but her speech development was normal. Other than one lower :,J
(')
respiratory tract infection, her past medical history was unremarkable. '"O
(')
:c
On examination, she was floppy and weak. While supine, her legs flopped outwards at
'"O
the hips. There was also paucity of leg movement. In ventral suspension, the child QJ
exhibited a rag-doll effect and head lag. She had muscle-wasting and tongue ;::l.
N
fasciculation. Her head circumference was on the 50111 percentile and her height and
weight on the 9 th percentile.
i. Spinal· muscular atrophy (SMA) type 2
ii. SMA type 1
iii. Scapulo-facial muscular dystrophy
Iv. Guillain-Barre syndrome
v. Duchenne muscular dystrophy
vI. Werdnig-Hoffman disease
vii. Prader-Willi syndrome
What investigations would help confirm your diagnosis?
i. EEG
ii. Spinal MRI
iii. CSF protein
iv. Survival motor neurone (SMN) gene-testing
v. Oligoclonal bands in CSF
vi. Muscle biopsy
vii. Creatine phosphokinase level
57
ANSWERS TO CASE 2. 7
a. i. Spinal muscular atrophy (SMA) type 2
b. iv. Survival motor neurone (SMN) gene-testing.
vii. Creatine phosphokinase
The diagnosis here is SMA type 2. The differential diagnosis includes congenital myo
tonic dystrophy, congenital nmscular dystrophy, congenital myopathy and congenital
OJ
neuropathy, although the fasciculation makes them unlikely. The diagnosis can be
::, confirmed by gene-testing for the SMN gene. Other investigations include creatine
a..
phosphokinase level, chrornosome analysis, TSH titre and urine amino/ organic acid
)>
::,
VI
concentrations.
(D SMA is an autosonial recessive degenerative disease of the anterior horn cells of the
'""I
VI spinal cord with loss of 1notor neurones leading to muscle atrophy. Three n1ain types
-+,
0
'""I
exist depending on age and acuteness of presentation. Overall incidence is 1 in 6000
r+ newborns. Usually presenting ,vith weakness, wasting and, often, tongue fasciculation,
::::,
(D all forms are progressive, with a shortened life expectancy due to respiratory cornpro
z
(D
rnise secondary to scoliosis.
.,
0
SMA type 1 (also known as infantile or Werdnig-Hoffinan disease) presents early; it
is usually obvious by 3 months of age and rapidly progresses. Affected infants die by
3 3 years. Infants have floppy paralysis below neck level. Facial and bulbar rnuscle strength
OJ
r+ is normal. Because of the paralysis of the intercostal muscles, respiration depends on
m the diaphragm.
><
OJ
3 SMA type 2 presents after 3 months of age. It runs a subacute course. Age at death is
widely variable, although survival into the 4th decade is recognized. Infants may appear
to develop normally and even stand before regressing. The n1ajority of children lead a
wheelchair existence.
SMA type 3 ( juvenile, Kugelberg-Welander) tends to present after 2 years of age with
pelvic and shoulder girdle weakness after a period of nom1al walking.
Mutations of the SMN gene (SMN1) are known to be responsible for SMA, particu
larly hornozygous deletion of exons 7 and 8 of the SMN1 gene on chromoson1e 5.
This is known to occur in 98% of all cases of SMA.
Prognosis depends on the type of SMA:
type 1 - 95% mortality by 18 months
type 2 - 60% mortality by 10 years
type 3 - mean age of death is 51 years
s:
;,;,
(')
.::,
(')
:c
.::,
0,
;:i.
N
Fig 2.8
A 6-year-old girl was admitted with vomiting, abdominal pain and bloody stools. An
ultrasound scan could not rule out an intussusception. After considered surgical review,
she went to theatre for a laparotomy. There was no intussusception but she appeared
to have large bowel colitis. She had no bowel surgery and returned to the ward. Stool
culture was sent and it was considered that she probably had an infective colitis. Her
FBe and U&E on admission were normal; 2 days post-operatively they showed:
Hb 9.5 g/dl
wee 19.4 x 10 9/I
ESR 2 mm/h
Na 134 mmol/I
K 4.4 mmol/I
Urea 11.8 mmol/I
ereatinine 80 µmol/I
Her urine output reduced and urinalysis showed her to have microscopic haematuria
but no proteinuria. Her blood film showed haemolysis with fragmentation of red blood
cells.
What is the likely diagnosis?
i. Henoch-Schonlein nephritis
ii. Amyloidosis
iii. Autoimmune haemolytic anaemia
iv. Shigella nephropathy
v. Post-infectious glomerulonephritis
vi: Haemolytic uraemic syndrome (HUS)
59
ANSWER TO CASE 2.8
vi. Haemolytic uraemic syndrome (HUS)
D With evidence of acute haemolysis, thrombocytopenia and deteriorating renal function,

C
(I)
the likely diagnosis is HUS. This is associated with Escherichia coli 0157 (which was
� isolated in this case) and can occur in epidemics. HUS occurs conm1only in children
o· younger than 4 years of age and is the n10st frequent cause of acute renal failure in
:J
Vl
children. Diarrhoea occurs for 5-7 days before haemolysis and thr01nbocytopenia
OJ
:J develop, and renal failure follows several days later.
0..
)> Management involves strict attention to fluid balance, renal function (focusing on
:J
Vl acid-base balance, hyperkalaemia and increasing creatinine), monitoring for and treating
�
(I) hypertension, and watching for fluid overload. As the haemolysis and anaemia deterio
""I
Vl rate, a blood transfusion may be required and this may exacerbate fluid overload. Thus
--+,
0
""I
transfusion has to be carefully considered. The child may go on to require dialysis as
.-+ renal function deteriorates.
::;
(I)
There is a good prognosis --with 65-85% complete recove1y. There is a mortality rate
z
(I) of 5-10% during the acute phase of the illness, and a fe,v patients develop end-stage
�
,,
0
renal disease.
3
OJ
.-+
m
X
OJ
60
A 12-year-old boy presented with difficulty breathing and abdominal pain. He had seen
the GP twice in the past with episodes of diarrhoea which subsided spontaneously. On
this occasion, the family mentioned a recent visit to a relative's wedding in central
s:
;::x:,
(')
Africa but said they had sought advice regarding immunisations and took prophylaxis "'t1
(')
against malaria. On examination, he was unwell, febrile and looked pale. There was I
dullness and decreased breath sounds in the base of the right lung. The right upper "'t1
0.,
quadrant was tender and the liver was palpable 4 cm below the costal margin. ;::i.
N
a. What are the most likely diagnoses suggested by this history and
examination?
SELECT THE TWO BEST ANSWERS
i. Right-sided pneumonia
ii Viral hepatitis
iii. fVlalaria
iv. Amoebic liver abscess
v Hydatid disease
vi. Typhoid
vii. Giardiasis
b, What investigations would best help confirm the diagnosis?
1. Blood gas
ii. Lung function tests
iii. CT scan
iv. Stool for microscopy and culture
v. Hepatitis serology
vi. FBC and film
61
ANSWERS CASE 2.9
a. i. Right-sided pneumonia
iv. Amoebic liver abscess
D b. iii. CT scan
C:
(I)
iv. Stool for microscopy and culture
�
o· The findings are consistent with an amoebic liver abscess. Differentials include a pyo
:::J
Vl
OJ
genic abscess and a right-sided pneun1onia.
:::J
0. Relevant histo1y would include change in bowel pattern, and histmy of diarrhoea and
)> dysentery, particularly while in Africa. It is, however, irn_portant to remen1ber that there
:::J
Vl is evidence of previous or concon1itant dysentery in only 50% of an10ebic liver
-
�
(I) abscesses.
�
A CXR may show a raised diaphragm. There may also be an effusion and other signs
.,r+0 of inflammation. An abdominal USS localizes and delineates the abscess in most cases.
:::; More than 95% of liver abscesses may be detected by CT scan. A FBC will usually
(I)
shavv leucocytosis. CRP /ESR is elevated. Serology is useful. Stools, if examined ,vhen
z
(I) fresh, will show signs of infection in about one-third of patients, usually amoebic cysts.
�
,,
0
Only in a minority are the amoebea demonstrable.
3
OJ
Metronidazole or tinidazole are the drugs of choice for the treatrnent of invasive
a1noebiasis. A lrnninal amoebicide is essential at the end of treatment for eradication
r+
m of amoebea fron1 the lun1en of the bowel. Broad spectrun1 antibiotics are indicated for
X suspected septicaemia.
OJ
3 Cmnplications include seconda1y bacterial infection, extension or rupture into the
peritoneal cavity, pleural cavity and or lungs. Blood-borne spread may result in a brain
or lung abscess.
62
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- _-+
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, -- +.
-_-
-
-
I
�
+---1----t-'---,--·--,·--•·--·-:----:··--:--- -: --_ :
J�4'.'.k��-r=-.C._::'tj
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- 1
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t
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-
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•i7 N
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Fig 2.10
An 18-month-old girl has been treated on the children's ward for meningococcal
septicaemia. This diagnosis has been assumed on the basis of a localised purpuric rash
and the growth of Gram-negative cocci on blood culture. She responds well to
intravenous fluids and antibiotics but after an initial recovery has developed increasing
tachypnoea. One of the investigations performed was an ECG.
What abnormalities can be seen on the ECG and what is the diagnosis?
Low voltage QRS complexes and raised 1. Second-degree heart block
ST segments 2. Cardiomyopathy
Sinus tachycardia with right heart 3. Pericarditis
strain 4. Prolonged QT syndrome
QTc of 0.55 s 5. Pulmonary hypertension
D. Right ventricular hypertrophy
E. Peaked T waves
ANSWER TO CASIE 2.10
A. and 3.
,0 The ECG shmvs low voltage QRS con1plexes in all the chest leads and raised ST
C
<D segments. This is consistent with diagnosis of pericarditis, a known complication of
� meningococcal infection. The pericardial effusion is generally purulent but may also
o· result frorn an autoimnrnne response and this typically occurs during the recovery phase
:::;
1/l
0)
of the illness.
:::;
a. An ernergency cardiac assessment should be obtained where possible as pericardiocen
)> tesis or surgical drainage n1ay be required as was the case with this girl (she had a
:::;
purulent effusion vvith tan1ponade). HO\,\rever, syn1ptomatic n1anagement may some
� tin1es be all that is required where the pericarditis and effusion have resulted from an
�
1/l
immune response as these generally prove to be transient reactions.
-+,
0
.......
,-+
ro
::::,
z
ro
�
-n
0
3
a.,
,-+
m
><
a.,
64
A 4-month-old child is admitted to hospital with pyrexia and irritability. She appears
unwell with decreased responsiveness and hypotonia. A septic screen is done and she is s;!
commenced on broad spectrum antibiotics. Blood, urine and CSF cultures are negative. :::0
n
Stool cultures grow adenovirus. Her blood film shows vacuolated lymphocytes. '"O
n
She recovers from the infection but on follow-up remains hypotonic with global I
developmental delay. Her weight is on the 50th centile and head circumference on the '"O
0,
90th centile. She is noted to have multiple Mongolian blue spots, coarse features, ;:::i.
peripheral oedema and hepatosplenomegaly. The fundi appear abnormal, and after N
pupillary dilatation, a cherry red spot is seen at the macula.
a. What diagnoses should be considered?
SELECT THE THREE BEST ANSWERS
i. Hunter's syndrome
ii. Tay-Sach's disease
iii. Niemann-Pick disease
iv. GM1 gangliosidosis
v. Gaucher's disease
vi. Cornelia De Lange syndrome
vii. Pseudohypoparathyroidism
b. What other investigations may be helpful?
i. CT head
ii. Cultured skin fibroblast enzymes
iii. Lateral spine X-rays
iv. EEG
v. Bone marrow examination
vi Karyotype
vii. Bone biochemistry
65
a. ii. Tay-Sach's disease
iii. Niemann-Pick disease
iv. GM1 gangliosidosis
b. ii. Cultured skin fibroblast enzymes
iii. Lateral spine X-rays
v. Bone marrow examination
OJ
g_ With children presenting like this, it is irnportant to seek further information from the
history; such as her developn1ental status before presentation, and whether there was
)>
:, any suggestion of developmental regression. Is there any parental consanguinity or
�
ro
fainily history of note? Does she startle easily to sound?
""'I
V,
Possible diagnoses to be considered include GMI gangliosidosis, Tay-Sach's disease,
-h
0
""'I
Sandhoff s disease, Hurler's syndrome, I cell disease and Niemann-Pick disease.
,-+
:s GMl gangliosidosis vvas the diagnosis in this child. This is an autosomal recessive
ro
condition due to deficient b galactosidase. There is accumulation within neurones and
z
ro viscera of con1pounds containing a terminal b galactosidase residue. This causes the
0
,, characteristic findings of coarse features, subcutaneous oedema, hepatosplenon1egaly and
progressive neurological deterioration. A cherry red spot on the retina is found in 50%.
3 The condition is associated with extensive and unusual Mongolian blue spots. Hypera
OJ
,-+ cus1s occurs.
m
>< White blood cell or cultured skin fibroblast enzyn1es are diagnostic. Lateral spine X-rays
OJ
3 may show anterior breaking. Bone marrmv examination reveals foamy cells.
66
s;:
;,J
(')
"'C
(')
:r:
"'C
OJ
;:i.
N
Fig 2.12
A 5-year-old boy presented with subcutaneous nodules in the right hand, right foot
and right ear. The lesions between his right index and middle fingers caused him
difficulty in writing. He was otherwise fit and well. He was born at 42 weeks'
gestation, symmetrically growth retarded with a birth weight of 2390 g. His neonatal
period was complicated by hypoglycaemia, thrombocytosis and a seizure. On
examination his height was between the 50th and 75th centiles and his weight was on
the 99.6th centile. He had a round face with narrow, slightly up-slanting palpable
fissures. An X-ray of the right hand (see above) showed multiple soft tissue areas of
calcification and ossification. The following investigations were performed:
Ca 2.44 mmol/I
Phosphate 1.35 mmol/I
ALP 566 mU/I
PTH 5.8 pmol/I (normal range 1.0-6.1 pmol/I)
TSH 2.7 mU/I (normal range 0.5-6.0 mU/I)
Thyroxine 105 nmol/I (normal range 70-180 nmol/I)
i. Pseudohypoparathyroidism
ii. Secondary hypoparathyroidism
iii. McCune-Albright syndrome
iv. Secondary hyperparathyroidism
v. Hyperparathyroidism
vi. Pseudopseudohypoparathyroidism
vii. Albright's polyostotic fibrous dysplasia
67
vi. pseudopseudohypoparathyroidism
0 Pseudopseudohypoparathyroidism (a type of Albright hereditary osteodystrophy) is the
C
(1)
most likely diagnosis. Confirmation can be nude by sending DNA for mutational
� analysis of GNAS gene.
o·
::i
VI Albright hereditary osteodystrophy (AHO) is a syndrome characterized by short stature,
OJ round facies, shortened 4th and 5th metacarpals/tarsals, and subcutaneous calcification.
:J
0.. AHO is often associated with pseudohypoparathyroidism (PHP), hypocalcaemia and
)> elevated PTH (PHP 1A) where PTH resistance leads to hypocalcaemia. Mental retarda
:J
tion is present in some cases.
�
(1)
"""I
VI
Patients with pseudopseudohypoparathyroidism have normal calcium n1etabolism and
-+, PTH levels with isolated AHO (phenotype).
0
"""I
,-+ Mutations in the GNAS1 gene which encodes the alpha subunit of the adenyl cyclase
::::;
(1) stirnulating G protein (Gsa), lead to features of AHO. Managing patients with AHO
z
<D
involves dietary advice, identifying learning difficulties at school and regular blood
� tests looking for PTH resistance. In patients with PHP, hypocalcaemia is treated with
0
,, vitamin D and calcium supplements aiming to suppress PTH levels into the normal
3
OJ
range.
,-+
m
><
OJ
68
An infant was born following a normal vaginal delivery at term. His mother was a
primigravida and was blood group O negative with no antibodies detected during
pregnancy. No resuscitation was required at birth. He bottle fed normally taking
adequate volumes of milk but was noted to be jaundiced at 12 h of age. The total
bilirubin was 250 µmol/I, blood group A positive and direct Coombs test negative. He
was commenced on phototherapy but the bilirubin continued to rise and he had an
exchange transfusion at 36 h of age when the total bilirubin concentration was
400 µmol/1.
a. What is the most likely cause of the jaundice and what other investigations
would help to confirm this?
i. Alpha thalassaemia
ii. Glucose-6-phosphate dehydrogenase deficiency
iii. Rhesus incompatibility
iv ABO incompatibility
v. Pyruvate kinase deficiency
vi. Hereditary spherocytosis
What other management steps are necessary?
1 Screening of siblings
ii. Iron supplementation
iii. Folate supplementation
iv. Careful monitoring of subsequent pregnancies because of increasing severity with
each pregnancy
v. Repeat Hb level
69
ANSWERS CASE 2.13
a. iv. ABO incompatibility
b. iii. Folate supplementation
0 v. Repeat Hb level
C
(I)
� Other investigations to confirm_ the diagnosis include a blood film_ and Hb to look for
o·
:::! evidence of haen10lysis. Group A haemolysin assay can be performed in the mother.
Vl
OJ
This test is not often performed as the diagnosis is usually obvious but if there is a
:::! doubt it can help to confirrn ABO incompatibility. Other causes of haemolysis such
0..
as glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency may
)>
:::! also need to be excluded, although these do not usually cause such a rapid rise in the
�
(I)
bilirubin in the first 24 h.
Vl The timing of this infant's jaundice suggests a haen10lytic cause. No antibodies were
detected during pregnancy so Rhesus disease or haemolysis due to other transfusion
,-+ related antibodies is unlikely. The direct Coombs test is also negative which is against
::::r
(I) a haen10lytic cause, but the combination of Group O in the mother and Group A in
z
(I)
the infant means that ABO incon1patibility is a possibility and severe haemolysis can
� occur with this condition despite a negative direct Coombs test. Anaen1ia in this condi
.,,
0
tion is usually only mild. The jaundice in ABO incompatibility is caused by A or B
3
OJ
haemolysins vvhich are IgG antibodies that can cross the placenta (unlike the usual A
or B IgM antibodies which cannot cross the placenta). The incidence of ABO incom_
,-+
m
patibility is 1 in 150 births, but severe disease is only seen in approxin1ately 1 in 3000.
>< The severity of ABO incompatibility is very variable and son1e infants will shmv very
OJ
3 little evidence of haemolysis despite a positive Coombs test, whereas other infants will
shov,1 severe haen10lysis and will require exchange transfusion. The Coon1bs test does
not indicate the severity of the condition. 40-50% of cases occur in first born infants
and it does not becon1e 1nore severe with subsequent pregnancies.
Repeat bilirubin checks are necessary until the level is under control. Folate supple
n1entation is needed, because of continued haen1olysis and follow-up to check for late
anaemia (although this is much less likely to happen than ,vith Rhesus hae1nolytic
disease). Late anaemia is ve1y unlikely in children with ABO incompatibility who did
not require an exchange transfusion.
70
1. Cystic Fibrosis 7. Fanconi syndrome
2. Wiskott-Aldrich syndrome 8. Diamond-Blackfan syndrome
3. Congestive cardiac failure 9. Partial anomalous pulmonary venous
4. Kartagener's syndrome drainage
5. Bartter syndrome 10. Congenital cystic malformation of the
6. Schwachmann-Diamond syndrome lung
the list above.
a. A 10-hour-old, male, term infant with a birth weight of 3260 g is noted to be
grunting. Antenatal progress had been uneventful, although situs inversus was
noted on the scans. The Apgar scores were 7 at 1 min and 10 at 5 min. No
resuscitation was required. On examination his temperature was 35.8° C, heart rate
130 bpm, respiratory rate 35/min. The oxygen saturation in air was 96%. He was
grunting and had a capillary refill time of 4 s. Heart sounds were normal and
femoral pulses were palpable. On chest auscultation there was bilateral and equal
air entry, with some intercostal recession. Blood gas was normal, and the grunting
settled with warming. However, he continued to have signs of respiratory distress
with tachypnoea, recession and an intermittent supplemental oxygen requirement
for several weeks. The CXR revealed scattered streaky shadows in the lung fields but
was otherwise normal. An ultrasound showed a structurally normal heart with a
left-sided liver and aorta.
b. A 3-month-old, breast-fed boy was seen in hospital. At 4 weeks of age, he had
been admitted to hospital appearing pale; he had Hb of 2.9 g/dl. He was also
neutropaenic. Extensive investigation revealed only that his lgM to EBV was positive.
At 3 months, he weighed 3760 g (birth weight 2960 g). His skin was dry and flaky,
and his stools were loose, pale and pungent. He had received two courses of oral
antibiotics from the GP for upper respiratory tract infections. CXR was normal.
Sweat test results were as follows:
volume of sweat obtained - 134 mg
sweat Na - 17 mol/1
sweat Cl -14 mmol/l.
c. A 6-month-old boy was referred by the GP with a cough and weight loss. He had
had a cough on and off since birth and vomiting for 2 weeks. His weight had
dropped from the 50th centile at birth to below the 3rd centile. The cough
sometimes produced green sputum. He was born at term and was well following
birth. He was admitted at 2 months with a persistent cough and blue episodes at
the end of coughing. A naso-pharyngeal aspirate was negative for respiratory
syncytial virus and after 5 days, he was sent home. On examination, he was afebrile.
Heart rate was 110 bpm, blood pressure 85/60 mm Hg. He was tachypnoeic, with a
respiratory rate of 40/min. His oxygen saturation was 86% in air. He had intercostal
recession, but a clear chest on auscultation. His skin was loose and he looked very
malnourished. Initial blood results showed:
Na 120 mmol/1
Hb 11.1 g/dl
K 2.3 mmol/1
wee 13.6 x 109/I
Urea 5.8 mmol/1
Creatinine 47 µmol/1
pH 7.579
Urine Na 5 mmol/1
Bicarbonate 40.5 mmol/1.
71
a. 4. Kartagener's syndrome
.0
C Persistent respiratory symptoms in the neonate ,vith no obvious cause and possible situs
ro
�
o·
::,
inversus suggest primary ciliary dyskinesia (PCD) and Kartagener's syndrome. PCD
denotes all congenital abnormalities of ciliary function whereas the tern-i Kartagener's
VI
syndrome refers to the subgroup of patients ,vith PCD and situs inversus. Persistent
0.>
::, moist cough or persistent and unexplained respiratory distress in the neonatal period
0..
should raise suspicion. Rhinitis or nasal congestion begins on the day of birth, persists
)>
::, and is difficult to treat. Although average presentation is at 16 years, nasal stuffiness
and heavy sputum production may have occurred since early childhood. Impaired
ro
"""'
VI
mucus clearance leads to severe sinopulmonary disease with chronic sinusitis, otitis
media with hearing impairment, nasal polyps and bronchiectasis. Most males are infertile
and females risk ectopic pregnancy. Rarer complications include hydrocephalus second
,-+
::::, ary to abnormalities of the brain ependymal cilia, complex congenital heart disease and
ro
biliary atresia. Diagnosis is by biopsy and treatment is similar to that used for cystic
z
ro fibrosis.
-n
0 b. 6. Schwachmann-Diamond syndrome
3
0.> Schwachmann-Diamond syndrome comprises cyclical neutropaenia, recurrent pyogenic
,-+
m
infections and pancreatic failure. 70% have thrombocytopaenia, 50% anaemia. Skin is
>< commonly dry and flaky, and is improved by pancreatic supplementation. Sweat Na is
OJ
3 normal. Inheritance is autosomal recessive. 25% go on to develop myelodysplastic
syndrome.
c. 1. Cystic Fibrosis
The most likely diagnosis is a pseudo Bartter syndrome caused by excessive sweat
electrolyte loss in undiagnosed cystic fibrosis (CF). In CF chronic sweat electrolyte loss
may be aggravated by an intercurrent illness, precipitating metabolic consequences.
There is a lack of adequate salt intake to counteract the loss through sweat. The bio
chemistry shows severe hyponatraemia, hypokalaemia and a metabolic alkalosis. The
hallmark of both Bartter and pseudo-Bartter syndrome is a very low serum Na and
potassium. The distinction between them is that there is no prima1y renal disease is
pseudo-Bartter syndrome. Extensive loss of serum electrolytes causes the kidneys to t1y
and reabsorb electrolytes in the tubules, and the loss of electrolytes activates the norm.al
compensat01y mechanisms, including the renin-angiotensin pathway. Vomiting may
have exacerbated the salt loss.
72
A 35-year-old asymptomatic Somali refugee mother living in the UK for 4½ years is
found on antenatal screening to be HBsAg positive.
Which of the following statements are true?
i. Hepatitis screening is unreliable in HIV +ve patients
ii. With a +ve HBe antigen, there is a 50% chance of mother-to-child transmission
iii. If mother is +ve for HBe antigen, the baby must receive hep B vaccination and
immunoglobulin at birth
iv. If mother is +ve for HBe antibody, the baby must receive immunoglobulin at birth
v. HBe antibody positivity confers protection against transmission to baby
vi. lmmunoglobulin must be given within 6 h of birth
vii. With no detectable HBe antibody, there is no risk of infectivity from the mother
viii. Neonatal hepatitis B vaccination is given in 2 doses
ix. Vertical transmission can be reduced by 40% by active immunisation at birth
x. Hepatitis B carrier status is associated with an increased risk of hepatocellular
carcinoma
73
TO 2.15
111. If mother is +ve for HBe antigen, the baby must receive hep B vaccination
and immunoglobulin at birth
I:)
C v. HBe antibody positivity confers protection against transmission to baby
(1)
x. Hepatitis B carrier status is associated with an increased risk of
�
a· hepatocellular carcinoma
::J
V>
OJ Carriers of HBsAg 1nay have hepatitis B e antigen present (high infectivity, up to 90%
::l n1other-to-child transmission in some studies), or antibody to HBe (10\v infectivity,
Q.
less than 5% perinatal transmission). Horizontal transmission between children also
)>
::J occurs.
� If the mother has HBsAg and HBe antibody present, the baby should be given hepatitis
.,
(I)
V>
B immunisation soon after birth and also at 1 and 6 n1onths. If HbeAg is present (or
-+,
0
., HBe antibody is not present), the child should receive hepatitis B imnmnoglobulin
...... within 24 h of birth, along with the immunisation schedule described. The immu
::::;
(I) noglobulin does not interfere with immunisation response.
z
(I) Vertical transn1ission can be reduced by 90% by active imnmnisation at birth.
�
-,, When hepatitis B is acquired as a neonate or infant, the risk of developing hepatitis B
0
3OJ carrier status is very high. Carrier status is associated vvith an increased risk of hepatic
cirrhosis and hepatocellular carcinoma in adult life, causing a n1illion deaths annually
......
m worldwide. The WHO recommends that all countries imnmnise for hepatitis B as a
>< part of their Expanded Program of Immunization (EPI), and currently, over 100 coun
OJ
3 tries have implemented this. Hepatitis B immunisation is not currently a part of the
routine imnmnisation schedule for children in the UK.
Any mother found to be positive for HbsAg should have her hepatitis B e antibody
status checked, and if negative the HBe antigen status should be tested. The mother's
liver function should be checked. She should be followed up, as we do not know how
recently she acquired infection, and she n1ay sero-convert. Antenatal screening should
also include offering testing for syphilis and HIV.
74
s:
:::0
(')
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()
:::r::
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OJ
;:::i
N
Fig 2.16
A 4-week-old boy presents to A&E with a small amount of bleeding from the umbilical
stump. The child is exclusively breast fed and though generally well, is noted to be
mildly jaundiced. He was born at term, birth weight 2800 g. The child is passing pale
stools, and the child is shown in the photo. The clotting screen demonstrates a
prothrombin time of 42 s (control 13), a partial thromboplastin time of 38 s (normal)
and a normal fibrinogen count. The total bilirubin was 93 µmol/I with a conjugated
bilirubin of 78 µmol/I.
The child's cx-1antitrypsin level is 0. 7 g/I (normal >1 g/I) and the phenotype is PIZZ.
What would you tell the parents regarding the child's prognosis?
i. The prognosis is usually worse in females
ii. The PIZZ phenotype is consistent with liver disease but rarely with pulmonary
complications
iii. There is a 50% chance that the baby will not have any long-term liver disease
iv. There is a 1 : 4 chance of any subsequent children being affected
v. There is a 50: 50 chance of any subsequent male children being affected
vi. Pulmonary manifestations occur before hepatic manifestations so he is unlikely to
suffer any respiratory problems
75
· ANSWERS TO CASE 2.16
a. iii. There is a 50% chance that the baby will not have any long-term liver
disease
iv. There is a 1 : 4 chance of any subsequent children being affected
When taking the history, it is irn-Portant to ask about the antenatal history: any infec
tions during pregnancy, consanguinity, and any family history of liver disease. One also
0,
needs to ask whether the child has had vitamin K. The most likely diagnoses would
::J be biliary atresia or a ·1 antitrypsin deficiency in view of the degree of cholestasis and
a..
the prolonged prothrombin time suggesting vitamin K deficiency. The intrauterine
)>
::J
VI
growth retardation in this context also suggests intrauterine infection or Alagille
syndrome.
ro
VI a-1 antitrypsin deficiency is the most common inherited cause of the neonatal hepatitis
-+,
...,
0 syndrorn.e, occurring in 1 : 1600-2000 live births in European populations. Prenatal
,-+ diagnosis by chorionic villous sampling is available. The children tend to have intrau
:::r
ro terine growth retardation, often severe cholestasis and differentiation from. biliary atresia
z can be difficult. Approximately 2% present with vitamin K responsive coagulopathy.
ro
� The major manifestation of AAT deficiency in the first 2 decades of life is liver disease;
-n pulmona1y manifestations appear later. The PIZZ phenotype is responsible for nearly
0
3 all cases of AAT emphysema and liver disease.
OJ
,-+ Initial emergency therapy should be initiated with the child being given parenteral
m vitamin K daily until the PT normalizes. If more severe bleeding develops, his coagu
><
OJ lopathy should be corrected inm1ediately with fresh frozen plasma. Thereafter manage
3 ment is supportive with nutritional intervention if failure to thrive occurs. Supplements
of fat-soluble vitamins are required and follow-up, usually on a shared care basis with
a paediatric gastroenterologist/liver centre, to monitor gro,vth, disease progression and
to ensure that further vitamin deficiencies do not occur.
Inheritance of a-1 antit1ypsin deficiency is autosomal recessive. There is a 1: 4 chance
of any future child being affected and there is a poorer prognosis in males. The prog
nosis in a-1 antit1ypsin deficiency is variable. Of those that present with early liver
disease, approximately 50% do well with no progression to long-term liver disease,
though some have a persisting transaminitis. In 25%, the liver disease progresses quickly
and they require transplantation in the first year of life. In the other 25%, the liver
disease progresses more slowly to cirrhosis and eventual decompensation requiring
transplantation.
76
A 12-day-old girl is admitted to hospital with a short history of poor feeding, lethargy
and jitteriness. She was born at term by normal vaginal delivery, with a birth weight of
3.5 kg and good Apgar scores. There were no risk factors for sepsis. The first day check
was unremarkable, and she was discharged home on day 2. Two days prior to this
admission, she was prescribed nasal drops by her GP for a snuffly nose. On
examination she is pyrexial, tachycardic with a pulse of 150 bpm, normotensive, and
has an oxygen saturation of 88% in air. Capillary refill time is 4 s. Cardiovascular
examination is otherwise normal. Her respiratory rate is 60/min, although air entry is
bilaterally good with minimal recession. Her abdomen is non-tender, with a 2 cm
hepatomegaly and a normal umbilicus. ENT examination is unremarkable. She has a left
exudative conjunctivitis but no rash. A self-limiting apnoea lasting 10 s was observed
during the examination. The initial investigations revealed the following:
Hb 17.5 g/dl
wee 5.1 x 109/I (neutrophils 2.3, lymphocytes 2.2)
CRP 17 g/I
Glucose, electrolytes and renal function were normal
CXR and urinalysis are unremarkable
CSF negative Gram stain
Blood is taken for culture. The baby is commenced on oxygen, i.v. fluids, cefotaxime
and gentamicin, and is observed on the high-dependency unit. On reassessment 6 h
after admission, the infant is still tachycardic with a pulse of 160 bpm and now requires
50% headbox oxygen. She has a 6 cm hepatomegaly. Further investigations are as
follows: AST 7305 IU/I, alkaline phosphatase 207 IU/I, total bilirubin 25 µmol/I,
PT >200 s, APTT >200 s.
What is the most likely diagnosis on reassessment?
i. Tuberculous meningitis
ii. Meningococcal meningitis
iii. Congenital heart disease
iv. lntracranial haemorrhage
v. Herpes simplex encephalitis
vi. Inborn error of metabolism
vii. cx1-antitrypsin deficiency
77
v. Herpes simplex encephalitis
On initial assessment, differential diagnosis must include bacterial sepsis (most likely
C
ro Group B streptococcal sepsis), HSV infection, intracranial haemorrhage and respiratory
�
o·:::l syncytial virus (RSV) infection. When there is no rapid improven1ent, further investiga
tions at this stage should include blood gases, LFTs, coagulation screen, cranial ultra
VI
ru
sound, eye swabs for microscopy, culture and sensitivity and for viral immunofluorescence
:::l and a nasopharyngeal aspirate to exclude RSV.
0..
)> The most likely diagnosis on reassessment is dissen1inated HSV infection, which causes
:::l
hepatic involvement and thus deranged LFTs and coagulation screen.
(])
"""I
VI Treatment is with high-dose intravenous acyclovir for 14-21 days. This child also needs
immediate aggressive management of the coagulopathy and intensive care management
of nrnlti-organ failure. In this case, HSV type 2 v_ras isolated from the eye swab and
r-+
::; CSF.
(])
z
(])
Up to 80c¾'i of women vvith genital herpes have no lesions at the time of delivery and
no known histmy of genital herpes and are not identified to receive preventive obstetric
"TI n1anagement or expectant paediatric input. Although the individual risk of HSV trans
0
3
ru
mission in this group is very small, more than 70% of cases of neonatal HSV arise from
this population of 1nothers. It follmvs, therefore, that, although a histmy of HSV in
r-+
m the mother is certainly helpful, its absence does not eliminate the risk of vertical trans
>< mission. Cutaneous manifestations of neonatal HSV infection (skin, eyes and mouth)
ru
3 require immediate intravenous acyclovir as there is a 70% risk of disse1ninated HSV
infection or encephalitis ,vithout treatment. Disserninated neonatal HSV infection
usually occurs in the first 14 days of life and typically presents with non-specific signs
such as poor feeding, lethargy and fever. There are no cutaneous manifestations in 50%
of cases. Dramatically elevated LFT results and a coagulopathy are common. The
mortality is 74% v,rith treatment. Disseminated neonatal HSV infection and antiviral
treatment should be considered in all potentially septic neonates presenting during this
period.
78
A 9-year-old girl is referred to the outpatient clinic with a 1-month history of weakness,
lethargy, weight loss and sore legs. She has had great difficulty climbing the stairs over �··.
.,,n
the past week, and her parents have resorted to carrying her. She is being bullied at :::0
n
school, and her parents think some of her symptoms may be psychosomatic. Further
::r:
.,,
symptomatic enquiry is unremarkable. On examination she has periorbital violaceous
erythema. She has a hoarse voice, is unable to lift her head off the pillow and has OJ
difficulty sitting upright. Cardiovascular, respiratory and abdominal system examination ;:::i.
is unremarkable. The upper parts of her arms and legs are tender on palpation. Arm N
abduction and elbow flexion are grade 3/5 bilaterally. Other arm movements are
normal. Hip flexion is grade 3/5 bilaterally, with otherwise normal leg movements. The
knee jerk is reduced bilaterally; the ankle jerks are both normal and the plantar reflexes
flexor. She is not ataxic.
Initial investigations revealed the following:
Hb 9.8 g/dl
wee 4.4 x 109 /I
Platelets 459 x 10 9/1
ESR 42 mm/hour
Na 138 mmol/I
K 4.2 mmol/I
Urea 2.9 mmol/I
Creatinine 55 µmol/I
i. Guillain-Barre syndrome
ii. Lyme disease
iii. Polymyalgia rheumatica
iv. Systemic lupus erythematosus
v. Dermatomyositis
vi. Still's disease
79
v. Dermatomyositis
0
C:
Derrnatomyositis is a systemic vasculopathy characterised by focal myositis and cutane
ro. ous findings such as periorbital violaceous erythema and papules over the extensor
� smfaces, including the classical Gottron's papules over the dorsum of the hand. Skin
o·
:::,
involvement ni.ay precede myositis, and the onset of proximal muscle weakness may
Vl
Q.l
be insidious and difficult to recognise, and may eventually manifest as difficulty in
standing or combing the hair. Upper airway muscle involvement may cause hoarseness,
a.
:::,
choking and aspiration. Im.paired gastrointestinal smooth muscle may precipitate con
)>
:::,
Vl
stipation, abdominal pain, diarrhoea and infarction. Cardiac conduction defects, dilated
cardiomyopathy, hepatosplenom.egaly, ocular involvement and seizures have also been
11)
V'l reported. Calcinosis is not uncommon at presentation.
-+,
0
., At diagnosis creatine kinase (CK), AST and lactate dehydrogenase are all elevated, and
,-+ antinuclear antibody is positive (speckled pattern) in 60%. The ESR may be normal
::;
11) or elevated, with a normocytic anaemia and lymphopenia commonplace. ESR and CK
z
11)
value can be used to monitor the response to treatment. A paediatric rheumatologist
� should supervise management. The diagnostic yield of electromyography and muscle
.,,
0
biopsy can be increased with the use of MRI to localise active disease, although these
3
Q.l
investigations are not needed when the diagnosis is clinically obvious, as in this case.
Steroids are the mainstay of treatment. Pulsed rnethylprednisolone is reserved for those
,-+
m with severe disease (respiratory and palatal involvement) at presentation. Methotrexate
X
Q.l
and cyclophosphamide are alternatives in cases unresponsive to steroid therapy. Dys
3 phagia may necessitate tubefeeding, and in rare cases of respiratory failure, tracheostomy
and ventilation may be required. Physiotherapy and. sunscreen are essential. With
aggressive i1m1rnnosuppressive therapy, the period of active symptoms is typically 18
months. The mortality is 3%, with long-term morbidity still under evaluation.
80
Fig 2.19
A 12-year-old boy is referred to A&E by his GP with a diagnosis of difficult asthma and
acutely worsening shortness of breath. He was relatively well until about 6 weeks ago
when he developed a dry cough and difficulty breathing, especially after exercise. There
is a family history of atopy. The family has two cats, and both parents smoke. Despite
being prescribed a salbutamol inhaler 6 weeks ago, he has also required two courses of
oral prednisolone for his respiratory symptoms, these being of benefit on both
occasions. He was started on becotide 200 mg two puffs twice daily 3 weeks ago.
Because of occasional fever, his GP prescribed a 3 day course of azithromycin 2 weeks
ago. Despite antibiotic treatment, his symptoms have progressed, and his mother says
that his breathing at night is becoming noisier and noisier. He has been sleeping sitting
up in bed for the past 5 days. On examination, he is afebrile with a pulse of 95 bpm
and a respiratory rate of 40 per minute. His oxygen saturation in air is 93%. His chest
is mildly hyperexpanded, and breath sounds are reduced bilaterally. There is a quiet
biphasic stridor and intermittent expiratory wheeze. Cardiovascular examination is
unremarkable. He has small mobile anterior cervical lymphadenopathy, an injected
oropharynx and a spleen palpable to 3 cm below the costal margin. His CXR is shown.
i. Hypertrophic obstructive cardiomyopathy
ii. Haemomediastinum
iii. T-cell lymphoblastic lymphoma
iv. Thoracic aortic aneurysm
v. Pulmonary embolism
vi. Bronchiectasis
81
ANSWERS CASE 2.19
iii. T-cell lymphoblastic lymphoma
The CXR shows a mediastinal mass, most likely to be a T-cell lymphoblastic lym
phoma. Investigations should include a blood film, tissue diagnosis (lymph node biopsy
and pleural aspirate), a bone n1arrow biopsy and a lun1bar puncture.
The presentation of non-Hodgkin's lymphoma (NHL) depends prin1arily on the site
ID of disease. T-cell lymphoblastic lymphoma n10st commonly (50-70%) prese11ts with an
:,
Cl.. anterior mediastinal mass. Local complications include compression of the intrathoracic
)> ainvay giving rise to respiratory compromise and biphasic stridor, and compression of
:,
Vl the superior vena cava causing SVC syndrome and pleural effusion. Rapid gravvth and
(1) early dissemination are typical of NHL so diagnosis, staging and initiation of treatment
'"'I
Vl must be prompt. Tissue diagnosis must be made and can sometimes be difficult if the
tumour is causing respiratory compromise as a general anaesthetic may be impossible.
..+ Diagnostic material can be obtained from pleural fluid, peripheral lymphadenopathy,
:::r
(1) bone marrmv or CSF. T-cell NHL and T-cell ALL represent a spectrum of disease.
z
(1)
By definition, if there is greater than 25% bone marrow infiltration the diagnosis is
T-cell ALL. T-cell lymphoblastic lymphoma is exquisitely sensitive to steroid therapy,
-n ·which will rapidly shrink a mediastinal mass. Tumour lysis syndrome is a common
0
3
OJ
consequence of treatment and with large mediastinal tumours may even occur pretreat
ment if the tumour mass outgrows its blood supply. Pre-treatment creatinine, uric acid
..+
m and lactate dehydrogenase (a marker of rapid cell turnover) need to be measured and
>< the size of mediastinal mass assessed on imaging. Pre-treatment intravenous hydration
OJ
3 and allopurinol are used to reduce the risk of tumour lysis syndrome.
82
A 2-week-old male infant was referred by his GP with a history of persistent vomiting,
poor feeding, irritability and weight loss. His parents had also noted that he had been
becoming increasingly drowsy over the previous few days. Examination revealed a
mottled infant with a capillary refill time of 4 s. He was hypotonic and difficult to rouse,
but apart from this, systemic examination was unremarkable. A full septic screen was
performed, and the baby was commenced on broad-spectrum antibiotics. Blood, urine
and CSF cultures were all negative. In view of this and the initial presenting picture, the
possibility of a metabolic disorder was raised.
Further investigations were undertaken.
Which of the following results would suggest a diagnosis of an inborn error of
metabolism?
i. pCO 2 of 6 kPa
ii. Serum Ca of 1.8 mmol/I
iii. Serum bicarbonate of 14 mmol/I
iv Ammonia 40 µmol/I
v. Lactate 0.8 mmol/I
v1. pH of 7.34
vii. Base excess -4 mmol/I
viii. Serum bicarbonate of 38 mmol/I
ix. pH of 7 .17
x. Blood glucose of 1.8 mmol/I
83
iii. Serum bicarbonate of 14 mmol/I
ix.pHof7.17
t:)
C: x. Blood glucose of 1.8 mmol/I
(I)
� Factors in the history which would suggest an inborn error of m.etabolism (IEM)
a· include poor feeding, irritability, persistent vomiting and drowsiness. Findings of n1.eta
::i
VI
OJ
bolic acidosis and hypoglycaemia, and possibly deranged LFTs (raised transaminases)
::i would also support this diagnosis.
a.
)> Management consists of the following:
::i
VI
� (1) Supportive care: intensive care if necessary; adequate respiratory support; the cor
(I)
"""I rection of hypothermia, hypoglycaemia and dehydration; monitoring electrolytes and
VI
- blood gases; the correction of any metabolic acidosis with intravenous sodium bicar
0 bonate (0.5-2 mmol/kg/hr); intravenous antibiotics as septicaemia is commonly associ
"""I
,-+
::s ated with metabolic decompensation.
(I)
z (2) Stopping all exogenous protein and giving intravenous glucose at 5-10 mg/kg/min
(I) in addition to insulin to promote anabolism and prevent catabolism.
�
-r, (3) Further treatment depends upon the diagnosis.
0
3 Although inborn errors of metabolism are a significant cause of mortality and morbidity
QJ
,-+ in children, with early recognition and appropriate treatment, the outcome can be good
m for many disorders. Making the correct diagnosis is also important in order to refer the
><
QJ
family for genetic counselling; prenatal diagnosis is offered for subsequent pregnancies.
3 An IEM should be suspected in a child of any age with any of the following: unex
plained acute encephalopathy; progressive neurological disease; acid-base disturbance
or hypoglycaemia; lactic acidaemia; certain dysmorphic features (e.g. Zellweger syn
drome); unexplained multi-organ or single-organ disease.
Metabolic investigations are divided into three stages. First-line investigations are those
which would normally be undertaken in any sick child but whose results may point towards
the diagnosis of an IEM - blood gas, sugar, electrolytes (increased anion gap), LFTs and
a full septic screen. Second-line investigations should be undertaken if an inborn error
of metabolism is suspected and should be considered early in the course of the disease.
Table 2.20.1
Second-line investigations Indications Comment
Blood ammonia Encephalopathy Normal <80 �1mol/l
Blood lactate Encephalopathy, acidosis Normal <2.5 mmol/1
Insulin, (-peptide, growth Hypoglycaemia Endogenous hyperinsulinisrn

hormone cortisol
Urinary reducing substances Liver/renal disease Unreliable for diagnosis of galactosaemia
Urinary ketones Encephalopathy, metabolic acidosis, Marked ketosis is unusual in newborn and
hypoglycaemia suggests an IEM
Acyl carnitines Encephalopathy, metabolic acidosis, Fat oxidation defects, organic acidaemias
hypoglycaemia, hyperarnmonaernia
Urinary/plasma amino acids Encephalopathy, hypoglycaemia, Aminoacidopathies, urea cycle defects

high ammonia level
Urinary organic acids Encephalopathy, hypoglycaemia, Fat oxidation defects, organic acidaemias
hyperammonaemia
Plasma carnitine Metabolic acidosis, hypoglycaemia, Primary and secondary carnitine deficiencies
cardiomyopathy, encephalopathy84
84
Beutler test Liver disease Screening for galactosaemia
A 4-year-old girl presented with 'excessive thirst'. She was drinking 3 I during the day
and waking at night asking for drinks. She was passing plenty of urine, but was not
enuretic. She is otherwise well and has a 2-month-old brother.
Investigations:
Na 134 mmol/I
K 4.1 mmol/I
Ca 2.2 mmol/I
A water deprivation test showed the following:
Serum osmolality 292 mosmol/I
Urine osmolality 930 mosmol/I
a. What further investigations/results are initially necessary?
i. CT head
ii. Serum glucose
iii. Glucose tolerance test
iv. Serum urea and creatinine
v. Renal ultrasound scan
vi. Urine microscopy and culture
i. Diabetes mellitus
ii. Excessive salt intake
iii. Nephrogenic diabetes insipidus
iv. Cranial diabetes insipidus
v. Psychogenic polydipsia
87
ANSWERS TO CASE 3.1
a. ii. Serum glucose
iv. Serum urea and creatinine
I:)
C: b. v. Psychogenic polydipsia
(I)
Vl
,-+ Diabetes mellitus is a possible diagnosis as it often presents v,1ith polyuria and polydipsia.
c5: On exan1ination, the child is not dehydrated and ketotic. It is excluded in this case by
:::s
Vl
Ill
measuring serum glucose.
c..
:::s
Chronic renal failure can present as polyuria (the kidneys are unable to concentrate
)> the urine, producing urine of low osrnolality) and consequent polydipsia. Features in
:::s
the history may be suggestive such as recurrent urinary tract infections, but may ,vell
�
(I) be absent.
"""I
Vl
-+, Diabetes insipidus (DI) is excluded as she is able to concentrate her urine during the
0
"""I ,�rater deprivation test. This test nmst be undertaken with care, as a patient with true
,-+
::J" DI can rapidly beco1ne dehydrated.
(I)
z
(I)
Psychogenic polydipsia is common and the most likely diagnosis. It may be the
� symptom of emotional disturbance, in this case, the arrival of a new baby in the
.,,
0
family.
3
Ill
,-+
m
><
Ill
88
s:;;c,
(i
ij
:c
(i
ij
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;::i.
N
Fig 3.2
A 12-year-old girl developed rapidly progressive, lower limb weakness over 2 days. She
initially noticed mild difficulties with walking and passing urine, despite the urge to void
and was then rendered unable to walk. On examination, there was swelling of the
optic discs, normal visual fields and otherwise no cranial nerve deficit. Power, tone,
deep tendon reflexes and sensation were normal in the upper limbs. In the lower limbs,
there were some anti-gravity movements in the hip flexors and adductors, but
otherwise flaccid paresis distally and bilaterally in all other muscle groups. Knee and
ankle jerks were s:><agge[ated with ankle clonus and extensor plantar responses.
Sensation was altered below a clear level at TS, with reduced perception of light touch
and pinprick but preservation of vibration and position sense. Her bladder was palpable
to the umbilicus; she was voiding small volumes of urine and therefore required
catheterisation. Three weeks previously, she had an illness comprising sore throat and
cervical lymphadenopathy. When questioned specifically, she could recall recently
having an insect bite on her leg. She had previously been healthy. Her maternal
grandmother had MS, diagnosed at age 18 years.
A lumbar puncture was performed after initial investigations. The results were as
follows:
CSF opening pressure 16 cm H2 0
CSF protein 0.3 g/I
CSF glucose 3.3 mmol/I
CSF microscopy 16 white blood cells/high power field - 100% monocytes
33 red blood cells/HPF
Her MRI spine is shown
i. Cerebral abscess
ii. Acute transverse myelitis
iii. Spinal space-occupying lesion
i v. Guillain-Barre syndrome 89
v. Polyneuritis
vi. Meningococcal disease
ANSWER
ii. Acute transverse myelitis (ATM)
Differential diagnoses include a spinal space-occupying lesion (secondary to tumour,
vascular malformation, abscess, haemorrhage or disease of the bony spine), or a vascular
infarction of the cord (seconda1y to nucleus pulposus embolism or the primary anti
phospholipid syndron1e). It is important initially to exclude spinal cord compression
which may require urgent surge1y.
Investigations include:
brain and spinal cord im.aging (to exclude spinal cord com.pression and raised intra
cranial pressure [before considering lumbar puncture])
lumbar puncture (in ATM, usually lymphocyte pleocytosis, variably elevated protein,
rarely more than three oligoclonal bands, norm.al glucose and pressure or CSF rnay
be normal; in Guillain-Barre syndrome, pleocytosis is unlikely)
PCR, CSF bacterial and viral culture, and intrathecal specific antibody serum serol
ogy throat swab, cultures of blood and stool
ANF, rheumatoid factor, partial thromboplastin time, anticardiolipin antibody and
antiphospholipid antibody
-n B12 and prothrombin screen
0
3
Ill
electrophysiology (may distinguish peripheral from. CNS lesion but can be confusing
early on if there is anterior horn cell involvement in ATM)
r-+
m
><
The MRI scan shows 111.ild swelling or enlargement of the cord on Tl weighted images
Ill over T2-9, and ill-defined and patchy increased signal in the cord.
3
ATM is a condition of cord inflammation which can follow various triggers:
post- or para-infectious inflammation (e.g. adenovirus, respiratmy syncitial virus,
influenza, measles, mumps and various vaccines)
true invasion of the cord - rare, but suspect if there are matching general symptoms
(e.g. varicella zoster, herpes simplex 1 and 2, Epstein-Barr virus, CMV, HIV,
various coxsackie viruses, hepatitis A, borrelia vincenti, mycoplasma pneumoniae,
yersinia enterocolitica, mycobacteria and parasites)
systemic lupus e1ythematosus/other connective tissue diseases; thrombosis due to
the anticardiolipin antibody
• lyme disease
The usual initial presentation in ATM is of senso1y symptoms and bladder dysfunction
with full-blown symptoms by 4 weeks. Severe back pain may occur at the beginning.
There is usually a definite sensory level (80% thoracic). Sensory loss is often dissociated
(loss of pain, temperature and light touch but preservation of position sense and vibra
tion). The degree of paraparesis varies considerably. Anterior horn cells may be involved
and reflexes may be reduced or absent, later brisk. GBS may be a differential diagnosis
when there is anterior horn cell involvement - tetraparesis and respirat01y muscle
involvement is more common, the sensory level usually less clear and early sphincter
involvement unusual.
Treatment: high-dose i.v. steroid pulse therapy over 3 days is promising but unproven
(dose regimen 20 mg/kg/day prednisolone or methylprednisolone). A pilot study has
suggested earlier and more complete recove1y with this regime. Rehabilitation should
be established early on. Urodynamics and nephrology expertise may be required in
cases of neuropathic bladder.
A 34-year-old known i.v. drug-abusing pregnant woman is found to be hepatitis C
antibody and PCR positive. She is negative for HIV and hepatitis B. She asks to speak to
you as the paediatrician for advice on the risks to the baby.
What advice should you give the mother?
i. There is no evidence that breast feeding increases the risk of chronic hepatitis C
infection in the child
ii. Fetal scalp blood monitoring should be avoided during labour
iii. Evidence suggests that the baby should be delivered by Caesarean section
iv. A positive hepatitis C antibody at 1 year of age is diagnostic of infection with
hepatitis C
v. There is a 20% risk of the child being chronically infected with hepatitis C
vi. Tests for hepatitis C can be carried out on the baby at birth (PCR)
vii. Hepatitis C virus is present in breast milk
viii. Hepatitis C antibody test at 6 months of age is diagnostic of infection
ANSWERS TO CASE 3.3
i. There is no evidence that breast feeding increases the risk of chronic
hepatitis infection in the child
,0
C ii. Fetal scalp blood monitoring should be avoided during labour
(I)
vii. Hepatitis C virus is present in breast milk
�
a·
::,
The risk of the child being chronically infected with hepatitis C is approximately
V)
0,
5%.
::,
a.. Presently, there is no con1pelling evidence suggesting that hepatitis C positive 111others
)> should have elective Caesarean sections to reduce the infection risk to the child, but
::,
it is probably advisable to avoid fetal scalp blood n10nitoring during labour.
""'I
V)
Despite a theoretical risk of infection from breast feeding (hepatitis C virus is present
--h in breast milk), there is no evidence that breast feeding increases the risk of chronic
0
""'I hepatitis C infection in the child. This must be tempered, however, with the fact that
r+
::; the studies have been relatively small and a small increase in risk would not have been
(I)
detected.
z
(I)
Possible tests are hepatitis C antibody and hepatitis C PCR on the child; hepatitis C
.,,
0
antibody at 18 months or hepatitis C antibody and PCR at 6 months (to be repeated
3 at 1 year if either is positive).
0,
r+ The prevalence of hepatitis C infection is as high as 80% in some drug-abusing popula
m tions. All present/past i.v. drug-abusing pregnant mothers should be screened for hepa
><
0,
titis C. The ideal testing policy for infants of hepatitis C positive 1nothers is difficult
3 as children who do not develop chronic hepatitis C can have hepatitis C antibody for
up to 16 months. Therefore, if one is to test for hepatitis C antibody alone, the test
should be deferred until the child is 18 months old. The hepatitis C PCR test has a
lo-w sensitivity in the first month of life, but its sensitivity increases to approximately
97% from 1 month. Thus, a combination of hepatitis C antibody and PCR could be
performed at 6 months with the proviso that if either were positive, then they would
have to be repeated later. The prognosis of chronic hepatitis C in children is unknown,
but hepatitis C is now the n10st common indication for adult liver transplantation.
There are presently paediatric trials of combination therapy in chronic hepatitis C with
interferon a and ribavirin. Although the treatn1ent is unpleasant, the sustained viral
clearance rates are likely to be similar to that in adults of -50%.
92
A 21-day-old male infant of consanguineous parents was referred by his GP with
collapse, vomiting and dehydration. He had no relevant antenatal history, and had been
born normally at term and breast fed. There were no dysmorphic features, and he was
estimated to be 10-15% dehydrated clinically. The infant was apyrexial, and there was
no rash. His capillary refill time was 8 s.
Initial tests reveal the following:
Na 116 mmol/1
K 7.9 mmol/1
Urea 18 mmol/1
Chloride 85 mmol/1
pH 7.08
pCO 2 4.7 kPa
Glucose 1.2 mmol/1
What are the key diagnostic tests of choice to be performed now?
i. Abdominal ultrasound scan
ii. Serum cortisol
iii. U&E
iv. Blood gas
v. Serum 17-hydroxyprogesterone
vi. Testosterone
vii. Urinary steroid profile
viii. Blood glucose
ix. Karyotype
93
v. Serum 17-hydroxyprogesterone
vii. Urinary steroid profile
,0
t:;: The most likely diagnosis here is a salt-losing crisis caused by congenital adrenal hyper
_ro
�
_o ·
plasia (CAH). The three cardinal features of this potentially fatal condition are hyponat
::l
rae1nia, hyperkalaemia and hypovolaemia, and this infant requires prom.pt resuscitation.
VI
OJ Acute v01niting resulting from sepsis is less likely.
::l
0.. CAH is a group of disorders. The most common is the defect caused by 21-hydrm7lase ..
)> deficiency (bet\veen 1/5000 and 15 000 births); it is more common in certain ethnic
::l
VI groups (Ashkenazi Jews). Other defects causing CAH (e.g. 11�-hydroxylase deficiency)
(1) are 10 ti1nes less frequent. 21-hydroxylase deficiency predisposes to crises as it affects
""'\
VI both cortisol and aldosterone production. A lowered cortisol level stinrnlates ACTH
-
0
""'\
production and consequent adrenal hyperplasia, the production of excessive androgens
r+ from. the adrenals causing virilization of fen1ales; boys usually appear normal.
::::,
(1)
The key diagnostic tests are serum 17-hydrm.7progesterone (17-OHP) and urinary
z
(1) metabolites of 17-0 HP. (You throw away ni.arks if you repeat urea and electrolyte
� tests, gas levels and glucose readings as you have already done them!) It will be neces
"Tl
0 sary to check that the child is male (and not a virilized female) by ultrasound of the
3
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genitalia and by karyotyping. Inheritance is autosomal recessive; careful family history
r+ should be sought and parental counselling given. Further tests for mutations in the
m 21-hydroxylase gene can be performed.
X
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3 This infant presented with hypovolaemic shock and initial management involved sta
bilising ABC; gaining i.v. access, and giving 20 ml/kg normal saline followed by a
glucose bolus and infusion. Broad-spectrum i.v. antibiotics must be given, and intra
venous hydrocortisone is life-saving. Essential further investigations include a FBC and
film, C-reactive peptide, blood and urine (SPA) cultures, and group and save. Urinary
electrolytes vvill be helpful in this case (a high sodium_ level will be noted).
Treatment cornerstones include the following:
Glucocorticoid replacement hydrocortisone is the usual choice in children, reduc
ing androgen production by inhibition of ACTH and corticotrophin releasing
harm.one. It has less effect on growth than do other steroids such as prednisolone
because of its short half-life.
• Mineralocorticoid replacement - if there is salt wasting, salt supplen1ents (about 6-
8 1mnol/kg/day) and fludrocortisone are the usual treatment regimen.
Surgery is occasionally used for genital an01nalies; the usual aim is to raise affected
children as their genetic sex, and in a few females clitoroplasty may be necessary.
Other - it is important to mention that these children and their parents will require
psychological counselling.
Follow-up - these children should preferably be referred to a paediatric endocrinol
ogy service as they will require life-long follow-up.
A 10-year-old prepubertal boy was diagnosed with a medullablastoma. He was treated
With surgery, chemotherapy and craniospinal radiotherapy (total cranial radiation dose:
5500 cGy). He was investigated for poor growth 2 years post-treatment with a
glucagon stimulation test.
TSH 1.3 mU/I (normal range 0.5-6.0 mU/I)
Thyroxine 67 nmol/I (normal range 70-180 nmol/I)
Comment on the results of the stimulation test (Table 3.5. i).
i. GH response within normal range
ii. A low peak GH response
iii. Inadequate glucose response
iv. No evidence of GH deficiency
v. Test inconclusive because of poor glucose response
vi. Adequate cortisol response (>double at 2 h)
vii. Satisfactory glucose response
Table 3.5.1
Time (�ins) Glucose (mmol/1) GH (mU/1) Cortisol (nmol/1)
0 4.5 4.5 85
30 7.5 B 140
o•~---�--•�--�r-
60 5.0 3.6 136
90 3.3 4.0 141
120 4.7
150 4.7
180 4.6 3.2 115

ANSWERS TO CASE 3.5
ii. A low peak GH response
vii. Satisfactory glucose response
.G
C
The test produced a satisfactory glucose response to glucagon with an initial rise of
�
(I)
blood glucose and. a fall of >2 mmol/1. The peak GH response is lmv at 6.4 mU/1
o·
:J (normal range >20 mU/1) signifying GH insufficiency.
Vl
0,
:J
Doses of cranial radiation in excess of 3000 cGy are ahnost all associated with GH
0.. deficiency v,rithin 5 years. There is a more variable outcome v.rith lower doses, with
)> some patients having neurosecretory dysfunction. The cortisol levels do not satisfy the
:J
criteria for an adequate response, i.e. low baseline value (nonnal range >120-150 nmol/
�
�
(I)
Vl
1), the cortisol level fails to rise 200 nmol/1 above the baseline and the peak value does
not exceed 500 nmol/1. This boy is at risk of both primary and seconda1y hypothy
-
0
� roidism. Dan1age to the thyroid gland may result from scatter radiation following spinal
r+ radiotherapy, which leads to prima1y hypothyroidism (raised TSH, low/norn1al thy
:::;
(I) roxine). Damage to the hypothala1nic-pituita1y tract from cranial radiation can lead to
z seconda1y hypothyroidism (lavv TSH, low thyroxine). This patient received GH,
<D
� hydrocortisone and thyroxine replacement.
.,,
0 Causes of abnormal linear growth include GH deficiency, hypothyroidism and hypocor
3OJ tisolaemia. He is also at risk of a subnormal pubertal growth spurt and a reduction in
r+ sitting height due to spinal radiation.
m
><
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3
96
A mother brings her baby to clinic for his 6-week check. This is her first baby and the
infant is bottle feeding on cows' milk formula. The mother is very anxious stating that
the baby cries constantly, does not feed and is not gaining weight. She thinks his milk
should be changed. On further questioning, you find that the infant was born at 34
weeks' gestation (birth weight 2.1 kg, 25 th centile) and spent 6 days on the special care
baby unit where there were no complications apart from jaundice requiring 24 h
phototherapy and nasogastric feeds for the first 2 days of life. The mother initially
attempted to breast feed but stopped after 2 weeks as she felt she did not have
enough milk. On examination, you find a well-looking, alert baby whose height, weight
and head circumference all lie on the 25 th centile.
a. What investigation must be done in this case?
i. FBC and U&E
ii. Thyroid function tests
iii. Stool for reducing substances
iv. pH study
v. Urine for microscopy and culture
vi. None
i. Lactose intolerance
ii. Gastro-oesophageal reflux
iii. Normal baby
iv. Coeliac disease
v. Cows' milk protein intolerance
97
TO CASE 3.6
a. vi. None
b. iii. Normal baby
In analysing feeding problems, it is irnportant to enquire about the food, the delivery
system and the recipient.
Food:
What type? (first or follow-on milk - advice may be required); how much? (overfeed
)> mg 1s a c01mnon problem); how often? (a frequent response to crying is to offer
::l
Vl milk).
([)
'""'I
Vl Delivery system:
-
0
'""'I Bottles may be difficult to clean - requires advice and suitable facilities; teats - need
,-+
::::, to adapt to suit the individual baby; are feeds being niade up correctly?
([)
z Recipient:
([)
�
,,
0
Babies vary son1e gobble and some are difficult feeders; the definition of infantile
3 colic is an otherwise well baby ,vith inconsolable crying for over 3 h a day.
OJ
,-+ It is also irn_portant to enquire about the mother's health and well-being. For instance,
m has she sufficient support and help ,vith caring for the demands of a newborn infant,
><
OJ
or has she syrn_ptoms of depression or other medical problems following the birth? Also
3 ask if there are any other features in the infant, such as vomiting, loose stools or con
stipation, skin rashes or any significant family history. The causes of feeding problems
which may be considered are as follows:
Concern the milk does not suit - Certain features may suggest cO\vs' milk hypersensitivity.
These include perioral swelling every tin1e milk enters the mouth, retching and von1it
ing after a feed and colic associated with loose, someti1nes blood-streaked stool. If this
is suspected, soya feeds n1ay be substituted but sensitivity to soya protein also occurs.
Lactose sensitivity may present with diarrhoea ,vhich continues after gastroenteritis.
Reg111gitation and 1Jomiting - It is important to note the timing of reflux in relation to
feeding, the volume lost, whether the infant seems uncomfortable and whether they
are thriving.
Anxiety that the infant is not getting enough - This is com1non and often leads to over
feeding, vomiting and further anxiety. Reassurance plus a careful analysis of the growth
chart to dernonstrate normal weight gain to the parents is helpful.
If, after careful questioning and exa1nination, there are no features to suggest any disease
in the infant, the correct managernent is maternal reassurance, addressing and allaying
her vwrries, together with support from the health visitor.
98
Fig 3.7
A 3-year-old girl attended with a 2-day history of sore throat, lethargy, anorexia, cough
and occasional vomiting but no diarrhoea. Initial vital signs were: temperature 39.6° (,
SaO 2 96% in room air, respiratory rate 35/min, pulse 140 bpm. She was lethargic but
interacted well. Her pharynx was injected. Chest examination showed symmetrical air
entry with no added sounds. The abdomen was soft, but with diffuse non-localised
tenderness. Neurological examination was normal. FBC showed a normal haemoglobin
and platelet count. WBC was 18 x 10 9/I with a predominant neutrophilia. A CXR was
performed.
What abnormality does the CXR show?
SELECT THE MOST LIKELY ANSWER
i. Cardiomegaly
ii. Round pneumonia
iii. Right atrial enlargement
iv. Mediastinal mass
v. Right middle lobe collapse
99
ANSWER TO CASE 3.7
ii. Round pneumonia
0 The CXR shows a well-defined, rounded, soft tissue opacity in the right lmver zone
C
(D
which is a 'round pneun10nia'. Round pneumonias are often caused by Streptococcus
� pneumoniae (pneumococcus). Most children ,vith pneun10nia can be managed as out
o· patients using oral therapy. For conm1-unity acquired pneumonia where pneumococcal
::,
VI
infection is suspected, amoArycillin is probably now the drug of choice. Indications for
OJ
::, inpatient care include systemic toxicity, underlying immune deficiency, dehydration,
Cl.
the need for OArygen therapy (SaO 2 <93%), social vulnerability and poor clinical
)>
::,
VI
response to initial treatment. Round pneumonias are usually located in the posterior
�
(D
and lower lobes of the lung. Their appearance and location may raise concern about
"""I
VI
the possibility of an intrathoracic tmnour, especially of neurogenic origin. Radiologi
-+, cally the edges of a round pneumonia are usually less well defined than those of a
0
"""I tumour, and an air bronchogram may be present. The typical clinical presentation and
,-+
::::, rapid response to antibiotic treatment such as benzylpenicillin or amoArycillin should
(D
make the diagnosis clear. Follow-up CXR, usually only justified in situations of initial
z
(D lobar collapse, n1ay give final reassurance.
�
-n
0
3
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,-+
m Admission criteria of pneumonia:
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3
Indications for inpatient care include
systemic toxicity, underlying immune
deficiency, dehydration, the need for
OArygen therapy (SaO2 <93%), social
vulnerability and poor clinical response
to initial treatment.
100
A 5-year-old boy was referred to the community paediatric services by his teacher.
Development in all areas was satisfactory until the boy started school. His teacher noted
that his academic progress had slowed, and he began to exhibit behavioural and
s:
;:,;,
(')
concentration difficulties. He also appeared to have hearing difficulties, and his speech '"tJ
(')
became less comprehensible. At presentation, he had severe problems affecting ::r:
receptive language, expressive language and speech sounds. His development in other '"tJ
Q)
areas appeared satisfactory. There were no concerns from his past medical or birth ::I
history. N
General and neurological examinations - satisfactory
EEG/sleep EEG - frequent left-sided epileptiform discharges, much more frequent
during sleep
Hearing assessment - normal
Cranial MRI - normal
What is the probable diagnosis?
i. Benign Rolandic epilepsy
ii. West syndrome
iii. Landau-Kleffner syndrome
iv. Mitochondrial myopathy
v. Lennox-Gastaut syndrome
101
ANSWER CASE 3.8
iii. Landau-Kleffner syndrome (LKS)
0 LKS, also known as acquired epileptic aphasia, is a rare form of childhood epilepsy
C
(I)
resulting in a severe language disorder. It usually develops between 3 and 8 years of
VI
age. In most cases, development is normal Llp to this age. The rate of development of
a·
r+
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this syndron1e is very variable. In young children who have not learned to talk, it may
VI
OJ
be n1istaken for a developmental language disorder, deafoess or autism. All children
:J with LKS have abnormal electrical activity in one or both temporal areas, the areas of
Q..
the brain responsible for processing language. Epileptiform activity is evident on EEG
)>
:J testing, particularly during sleep. Approximately two-thirds of children have night
� seizures.
�
VI The language disorder usually affects comprehension. Many children have difficulty in
--t,
0
"""I
understanding their own name. They are also likely to have difficulty recognising
r+ environmental sounds such as a ringing telephone. These children may appear to be
:::Y'
<D deaf Expressive language can also be affected, and some children cornpletely lose their
z
<D
speech. A child may rarely understand language but have difficulty speaking.
� Behavioural problen1s especially hyperactivity, poor attention, depression and irritabil
"TI
0 ity, are common. Some have episodes of very abnormal 'autistic type behaviour'. The
3 behaviour, seizures and the epileptiforrn EEG usually resolve by early adolescence.
OJ
r+ Some may fully recover their language, but many are left with a disability. Paediatric
m neurology referral is required. Referral should also be made to the speech and language
><
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therapist and educational psychologist.
3
Treatment options include steroids, antiepileptic drugs and neurosurgery.
Antiepileptic drugs are used to treat seizures but may not affect the EEG abnonnalities
in the long term_. Steroids taken early or for a sufficient time often improve the EEG
findings and allow language to recover. For those who do not respond to these
measures, neurosurgery (multiple subpial transection) may be appropriate. Appropriate
speech and language therapy and special education are essential.
An introduction to sign language may be required.
102_
A 14-year-old boy arrived in hospital with status epilepticus. He had had surgical repair
of a lumbosacral myelomeningocoele in infancy and had had a decompression of the
foramen magnum for Arnold-Chiari malformation 2 months before this admission. The
seizure was treated with intravenous diazepam and phenytoin. On examination, he was
agitated with a Glasgow coma score of 9, pulse 70/min and his blood pressure was
200/120 mm hg. His electrolytes were as follows:
Na 137 mmol/I
K 4.1 mmol/I
Urea 21 mmol/I
Glucose 10.5 mmol/I
,What is the likely cause of his raised blood pressure?

i. Hypertensive encephalopathy secondary to chronic renal failure
ii. Raised intracranial pressure secondary to obstructive hydrocephalus
iii. Phenytoin ingestion
iv. Acute tubular necrosis secondary to poor renal perfusion in status epilepticus
103
ANSWERS CASE 3.9
i. Hypertensive encephalopathy secondary to chronic renal failure
This boy had hypertensive encephalopathy secondary to chronic renal failure. In his
case, the most likely cause of renal failure is obstructive uropathy caused by a neuro
pathic bladder.
A CT head scan should be performed to look for signs of raised intracranial pressure
or post-operative complications, e.g. bleeding. This will necessitate intubation and
ventilation in view of his reduced conscious level and agitation.
A labetolol infusion is used to treat the hypertension by a controlled reduction, initially
at a rate of 1-3 mg/kg/h. Invasive monitoring of blood pressure via an arterial
line may be required. Other drugs used include hydralazine and nifedipine. This
boy also requires catheterisation and is likely to need long-term intermittent
self-catheterisation
.,,
0
3OJ
,-+
m
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3
104
An 11-year-old boy was referred by the school nurse for investigation of his short
stature. He was born on the 50th percentile for height but on presentation was below
the 3 rd percentile. As a baby, he suffered from gastro-oesophageal reflux, recurrent
s:;JJ
(")
vomiting and failure to thrive. He walked at 20 months. He was thought to be clumsy "'t1
(")
and diagnosed as dyspraxic. General examination revealed a prominent chest, low
posterior hairline and small-volume testes. His bone age was 8 years. "'t1
Ill
a. What is the probable diagnosis?
�
N
i. Angelman syndrome
ii. Prader-Willi syndrome
iii. Mitochondrial cytopathy
iv. Beckwith-Wiedemann syndrome
v. Noonan syndrome
vi. William's syndrome
b. What other investigation is essential?
i. Abdominal ultrasound scan
ii. Growth hormone
iii. Electroencephalogram
iv. Echocardiogram
v. Serum Calcium
105
a. v. Noonan syndrome
b. iv. Echocardiogram
Noonan syndrome was first described in 1963. The overall incidence of the condition
is between 1: 1000 and 1: 2500 live births. Although the inheritance is autoson1al
dominant, many cases are sporadic. A gene mutation of the PTPN11 (protein-tyrosine
OJ phosphatase, non-receptor-type 11) gene underlying this condition has been located
::J on chromosome 12 and is found in about 50% of cases.
a.
)> Noonan syndrome is a clinical diagnosis. It is characterised by dysrn.orphic facial features
:l
VI (hypertelorisrn., downwards-slanting palpebral fissures, ptosis, low-set and posteriorly
� rotated ears, a low posterior hairline and a short neck), short stature and cardiovascular
�
anorn.alies (pulrnonary valvular stenosis, hypertrophic cardiomyopathy and atrial septal
-h
0
., defect). Chest deformity (pectus carinatum/excavatun1), low-set nipples, cryptorchidism,
r+ mild n1.otor delay and learning difficulty are also frequent associations. Bleeding dia
::::r
(I) theses (a prolonged APTT and various coagulation factor deficiencies), gut dysmotility,
z
(I)
hearing and visual abnormalities can also occur. Developmental co-ordination disorder
� (previously known as dyspraxia) occurs in more than 50% of affected children.
"TI
0 GH treatment improves height velocity in the short term. Long-term treatment has
3
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not, however, substantially improved final height.
r+
m
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106
Fig 3.11
A 3-month-old male infant presented with failure to gain weight. There was no family
history of note and the parents were not consanguineous. He was born full term and
weighed 2700 g (9th centile). His head circumference and length were also on the 9 th
centile at birth. At 3 months, he weighed 4000 g, well below 0.4th centile, as were his
head circumference and length. He was admitted to the ward for observation and
assessment. He fed extremely well and took up to 200 ml/kg/day of bottle milk. On
examination, he appeared dysmorphic. He was neither cyanosed nor icteric. He looked
well and was not breathless at rest. He had a grade 2/6-ejection systolic murmur at the
upper left sternal edge. His peripheral pulses were normal. He had a soft 2 cm liver
edge palpable. His abdomen was not distended. He had normal tone and he was
developing normally. Initial LFT showed:
ALP 1094 IU/I (100-300)
AST 100 IU/I (545)
Gamma GT 670 IU/I (10-120)
Bilirubin 8 µmol/I (1-22)
Total protein 74 g/I (55-75)
Albumin 45 g/I (35-50)
What is the likely syndrome?
i. Rubinstein-Taybi syndro�
ii. Schwachmann syndrome
iii. a1-antitrypsin deficiency
1v. Alagille syndrome
v. William's syndrome
107
iv. Alagille syndrome
0 This child is dysmorphic with deep-set eyes, a broad forehead, bulbous nose and
C:
f£a·
prominent chin. He has poor growth and has an obstructive pattern to his LFTs. He
has a cardiac murmur loudest in the puhnonary area. These features suggest Alagille
:::,
syndrorne (arteriohepatic dysplasia). Symptoms include an intrahepatic paucity of bile
V'l
0,
ducts with subsequent cholestasis, and a pulmonary artery stenosis, although patients
::::s can have atrial or ventricular septal defects or coarctation. Alagille syndrome patients
c.. have eye abnormalities including a posterior e1nbryotoxon (prominence of Schwalbe's
)>
:::,
V'l
line). They may p.ave reduced renal function with raised uric acid. If there were any
�
<D
doubt in his syndromic diagnosis, other causes of cholestatic liver disease would need
to be explored .
-+.
0
.., Nutritional assessment is mandatory with particular focus on fat-soluble vitamins. Sup
r+ plementation of these vitamins (A, D, E, K) is essential. Clotting studies should be
:::,
<D checked. Hypercholesterolaemia is often associated with the syndrome. Review by a
z hepatology team is also required; ultrasound of the liver will confirm if there is an
<D
� extrahepatic bile system_ and consideration for liver biopsy at s01ne stage is required to
.,,
0
demonstrate the biliary hypoplasia. Fluorescence in-situ hybridisation studies may dem
3
0,
onstrate a deletion on chromosome 20p. The family will need genetic consultation.
Ophthaln1ology assessment is required. Cardiac assessn1ent in this case revealed a bilat
r+
m eral branch puhnona1y arte1y stenosis, which was uncomplicated. Renal function needs
><
0, to be rnonitored and some children may get further growth retardation seconda1y to
3 reduced GH or hypothyroidism.
Pruritis due to increased serum_ bile acids can cause major discomfort to the child.
The management options are: ursodem,ycholic acid (10-20 mg/kg/day divided),
phenobarbitone (3-5 mg/kg/day), rifampicin (3-10 mg/kg/day) or trimeprazine (dose
dependent on age).
108
A baby boy was born at term in good condition, Apgar score 9 at 1 min and 10 at
10 min. He was transferred to the special care baby unit on day 2 with poor feeding, s:
::0
vomiting and lethargy. A full septic screen including lumbar puncture was performed ()
and antibiotics commenced. -0
()
:c
Over the next 12 h he deteriorated and required intubation for apnoeas. He -0
OJ
subsequently had several right-sided seizures. He was noted to have 3 cm '""I
..+
hepatomegaly and to be hypotonic. He was thoroughly investigated; results included N
ammonia 2500 µmol/I (normal 10-40) and raised serum and urine citrulline.
a. Which group of metabolic disorders does this condition belong to?
i. Organic acidaemias
ii. Mucopolysaccharidoses
iii. Mitochondrial cytopathies
iv. Mucolipidoses
v. Urea cycle disorders
vi. Glycogen storage diseases
vii. Fatty acid oxidation defect
b. How could you manage his acute hyperammonaemia?
i. Forced alkaline diuresis
ii. Stop intake of protein
iii. Sodium phenylbutyrate
iv. High protein diet
v. TPN
vi. Sodium bicarbonate
.109
ANSWERS CASE 3.12
a. v. Urea cycle disorder
b. ii. Stop intake of protein
iii. Sodium phenylbutyrate
This child has citrullinaernia, one of the urea cycle disorders. Abnormalities in the urea
cycle create increased levels of ammonia, which cannot be metabolised. Urgent man
agement is required to reduce these dangerous levels of ammonia. Measures include:
Stop exogenous protein
Inhibit catabolism of protein by giving maintenance glucose infusions, correcting
any metabolic acidosis, reversing any hypothermia and treating seizures with anti
convulsant medication
Use i.v. drugs to convert nitrogen to an excretable product: sodium benzoate,
sodium phenylbutyrate and/ or arginine can be used
Dialysis (haemodialysis or peritoneal dialysis) is used if urine output is poor, ammonia
,-+
:Y levels are very high, or there is inadequate response to i.v. therapy
(D
z
(D
Long-term management involves the use of a low-protein diet, an emergency high
calorie regime during intercurrent illnesses to prevent protein catabolism and the use
,,
0
of oral medication to aid nitrogen excretion (e.g. arginine, sodium benzoate). Long
3
QJ
term prognosis, particularly in terms of mental handicap, is related to the avoidance of
severe hyperammonaemia.
,-+
m
><
QJ
110
A baby boy born at 33 weeks' gestation by normal vaginal delivery became septic on
the 7 th day of life and his CSF grew group 8 �-haemolytic streptococcus. On day 12 he
was noted to have the following blood results:
Na 165 mmol/1
K 4.5 mmol/1
Urea 6.8 mmol/1
Cre;:itinine 52 pmol/1
Cortisol 28 nmol/1 1 in three consecutive samples)
TSH 3.54 miU/1
FT4 6.9 pmol/1
i. Iatrogenic sodium overload
ii. Acute tubular necrosis
iii. Bartter syndrome
iv. Adrenal ischaemia
v. Panhypopituitarism
vi. Syndrome of inappropriate ADH secretion
i. Panhypopituitarism
This baby's blood results show hypernatraern.ia, with low cortisol and low thyroid
hormone levels. This is consistent with a diagnosis of panhypopituitarism with diabetes
insipidus. The cause of this is the group B strep meningitis.
Management involves replacement of deficient hormones - hydrocortisone and thy
OJ roxine (oral preparations) and desmopressin (synthetic analogue of arginine vasopressin
a.
::,
which has a prolonged antidiuretic effect and almost absent pressor activity) for diabetes
)> insipidus. The route of administration for desmopressin could be intranasal or oral. The
::i
V) oral preparation,. however, is not as effective as the nasal preparation.
(I)
-,
V)
General advice should be given to the carers regarding intercurrent illness, stress or
-+, physical effort, which will increase the require1nent of hydrocortisone. Training must
0
-, be given to parents and registration with the local paramedics is required for adminis
,-+
::; tration of intramuscular hydrocortisone which is needed prior to reaching the hospital
(I)
in cases where the child has a serious illness (e.g. fractured fenmr, sepsis, etc.). The
z
(I) foremost rule in the treatment of diabetes insipidus is that the child should have access
�
,,
0
to water or fluids. This is more important in infancy when the child is unable to ask
for water. The family must be informed that during the replacement therapy the child
3 is unprotected against excess water. If severe ill health occurs during combined hydro
OJ
,-+ cortisone and ADH treatrn.ent then stop the DDAVP treatment during the period of
m steroid dose increase, and restrict fluid intake to avoid dilutional hyponatraemia - restart
><
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the DDAVP only when a diuresis occurs.
3
Education of the family is of prime importance. A Medic-alert bracelet with the diag
nosis and treatment is strongly recommended.
112
s::
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(")
"'O
(")
::c
"'O
""
ru
r+
N
Fig 3.14.c
Fig 3.14.b
Fig 3.14.a
A 5-year-old girl with CF underwent a heart-lung transplant. At the regular review in

the outpatient clinic, she presented with the features illustrated in Figure 3.14.a, b.
a. What is the aetiology of these features?
Vitamin A deficiency
i1 CF related disease
iii Graft versus host disease
1 lmmunosuppressant therapy
T • 2e years after the transplant, she presented with history of progressive shortness of
b ·ath and a reduction in exercise tolerance, and this CT scan (Fig. 3.14.c) was
p formed.
t What is the most likely diagnosis?
i. Obliterative bronchiolitis
ii. Allergic bronchopulmonary aspergillosis
iii. Pulmonary oedema
iv. Pneumocystis carinii
113
3.14
a. iv. lmmunosuppressant therapy
b. i. Obliterative bronchiolitis (OB)
The features illustrated are hirsutism, nasal polyps and gingival hypertrophy. All three
are cyclosporin-related side-effects, although nasal polyps may also be found in CF.
Manage1nent options include the practical measures of use of a depilatory crean1, gum
shaving and polypectorn.y, while maintaining the patient free from rejection on a
minimal dose of cyclosporin. An alternative would be switching cyclosporin to tac
rolimus (FK 506). Both have a sim.ilar mechanism of action (inhibiting T-cell synthesis
of lymphokines, hence activation and proliferation of cell-rn.ediated cytotoxicity and
humoral immunity) but changes to physical appearance are not a side-effect of
tacrolimus.
-+,
0
"""I
OB is the pathological hallmark of chronic graft dysfunction. The CT scan demon
,-+ strates bronchial dilatation, decreased peripheral vascular markings and a hyperinflated
::,
([) chest. These findings are most consistent with a diagnosis of OB. There are many
z
([)
processes (allo-immune and non allo-imnmne) which lead to fibrotic obliteration of
airway lumen. The average time to onset or diagnosis is 16-20 months but the range
""T1 can be very broad. The clinical presentation can be acute and imitate infection, or
0
3
OJ
insidious with a progressive decline in lung function. The diagnosis of OB is comple
mented by transbronchial biopsy and spirorn.etry. Recurrent acute rejection is the most
,-+
m significant risk factor. CMV infection or pneumonia is also believed to be a predispos
X
OJ
ing factor. But the precursor pathophysiology is not clear. Once OB has occurred, it
3 is rarely fully arrested by therapy and the response is often transient.
Managen1ent consists of imnrnnosuppressant therapy. In the UK, the most widely used
triple immunosuppressant regimen is cyclosporin, azathioprine and prednisolone.
A baby weighing 1800 g was born by emergency Caesarean section for pregnancy
induced hypertension at 31 weeks' gestation. From day 4 of life, he became
progressively jaundiced. He had mild respiratory distress syndrome, presumed
necrotising enterocolitis that was being treated conservatively, and had received total
parenteral nutrition. He was the first child of healthy parents, and the mother's blood
group was O positive. His length and weight were below the 0.4th centile, and his head '"ti
a,
circumference on the 2 nd centile. Examination revealed a splenic tip and a 1 cm smooth �
liver edge. N
His blood tests on day 20 were as follows:

Haemoglobin 16. 7 g/dl
Total bilirubin 151 µmol/I
Conjugated bilirubin 132 µmol/I
ALP 350 IU/I
ALT 58 IU/I
Albumin 28 g/I
There is one important diagnosis which initially needs excluding; what
investigation would need to be carried out to exclude this?
i. Coagulation screen
ii. Urobilinogen
iii. Liver biopsy
iv. Hepatogram
v. Liver ultrasound scan
vi. HIDA scan
vii. Fungal blood cultures
ANSWER TO CASE 3.15
vi. HIDA scan
,0 The differential diagnosis includes sepsis, biliary atresia, TPN-related hepatitis, and
C
(I) physiological jaundice. Prolonged i.v. nutrition causes cholestasis and hepatocellular
� damage, which may progress to cirrhosis. Prevalence increases with the degree of
5· pren1aturity, degree of intra-uterine gravvth retardation and duration of parenteral
:::i
VI
OJ
nutrition. Sepsis, hypoxia, intraabdominal surgery and hepatotoxic drugs aggravate the
:::i damage.
0..
)> Other important factors from the history are stool colour and urine colour. This is to
:::i
help differentiate between obstructive and non-obstructive jaundice. In obstructive
�
(I) jaundice, the stools would be pale and the urine would be dark.
"""I
VI
-+, Biliary atresia is the condition which needs prompt diagnosis as if caught early enough
0
"""I it is arnenable to treatment. This is a destructive sclerosing inflammato1y process
,-+
:::, extending from the extrahepatic biliary tree to the intrahepatic ducts. Its incidence is
(I)
approximately one in 14 000 live births. Prevalence is the sa1ne in premature and term
z
(I) babies. Surgical correction (Kasai operation) by 60 days of age is the gold-standard
�
.,,
0
treat1nent. Surge1y is usually postponed until the baby reaches 3000 g, as the risk of
surge1y is too great earlier. Either a Kasai operation may be carried out or a liver
3
OJ
transplant performed. Investigations which may be performed to help confirm bilia1y
,-+ atresia include a bilia1y ultrasound scan, a HIDA scan and a percutaneous liver
m
><
biopsy.
OJ
3
116
Fig 3.16.A
Fig 3.16.B
A 16-week-old boy was seen by a paediatrician after paucity of limb movement was
noted at an 8-week check. Pregnancy and birth were uncomplicated; no problems were
noted. Feeding was difficult and slow. Examination showed the boy to be strikingly
floppy, lying in frog-leg posture, with little spontaneous movement (he could move his
limbs against gravity); marked head lag was noted, his mouth hung open with tongue
protruding. Liver was 1 cm enlarged. Chest and cardiovascular examination appeared
clinically normal. CXR and ECG are shown. Other tests were as follows: CK 1282 units/I;
AST 426 units/I; CKMB 40 units/I; CKMB/CK ratio 3%.
a. Describe the abnormalities in the electrocardiogram
i. Superior axis deviation
ii. Right atrial hypertrophy
iii. Biventricular hypertrophy
iv. First degree heart block
v. ST depression
vI. Inferior axis
vii. Prolonged QT
viii. Reverse RSR'
b. What further investigations are needed?
i. Muscle biopsy
ii. Echocardiogram
iii. EEG
iv. CSF for oligoclonal bands
v. White cell enzyme assays
c. What is the likely diagnosis?
SELECT ONE ANSWER
i. Hypertrophic obstructive cardiomyopathy
ii. Mucopolysaccharidosis
iii. Glycogen storage disease type II (Pompe's disease)
iv. Acute demyelinating encephalomyelitis
v. Spinal muscular atrophy
vi. Gaucher's disease
117
TO CASE 3.16
a. ii. Right atrial hypertrophy
iii. Biventricular hypertrophy
vi. Inferior axis
b. ii. Echocardiogram
v. White cell enzyme assays
c. iii. Glycogen storage disease type II (Pompe's disease)
.OJ
:::,- The CK is very high (norm.al range is up to 195 units/1). CKMB is also marginally
0..
raised (normal range is up to 25 units/1). CK.MB/CK ratio is within norrnal range
)>
:::,- (nom1al range is up to 6%) indicating that the very high CK level is mainly of skeletal
� muscle origin.
�
Further investigations should include an echocardiogram and white cell enzyme
-
0
""'I
assays.
,-+
:::::, The diagnosis is glycogen storage disease type-II (Porn.pe's disease, infantile acid maltase
(1)
deficiency). Children with Pon1pe's disease usually die within the first 2 years of life
z
(1) due to rapidly progressing cardiomyopathy or aspiration pneumonia leading to cardio
� respirat01y failure.
-r,
0
3
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Glycogen storage disease type-II is an autosorn.al recessive condition and, in the
infantile variety (Pompe's disease), there is deficiency of a lysosomal enzyrn.e 1,4
,-+
m alpha-glucosidase. It characteristically presents in the first month of life with profound
>< hypotonia, massive cardiorn.egaly, hyporeflexia and macroglossia. In this child, 1,4 alpha
OJ
3 glucosidase was found to be ve1y deficient, confirming the suspicion of Pompe's
disease.
Physical signs in Pompe's disease include: hypotonia, progressive weakness, absent
reflexes, hepatomegaly and cardiomegaly.
Fifteen-year-old John developed a sore throat on a school skiing holiday in Switzerland.
He had also had a sore throat 2 months before. On returning to the UK, a widespread
non-itchy rash appeared. The day before, he had had a little neck stiffness which had
totally resolved overnight. John's best friend had the same problems during the holiday.
John's temperature was 36 °C. Heart rate and blood pressure were normal. The rash
was pink, macular and blanching. His tonsils appeared reddened. The rest of his
examination was normal.
John was asked to return 2 days later for review. The rash had spread further, but did
not involve his face. Otherwise, he was entirely well, afebrile and the rest of his
examination was again normal. Results from the initial presentation were: Hb 12.8 g/dl,
WBC 28 x 109/I, neutrophils 25.2 x 10 9/I, platelets 272 x 10 9/1, CRP 243 mg/I,
Monospot negative. The throat swab had disappeared.
Blood tests were repeated.
The health authority contacted the family, as another child from the school skiing
holiday had been hospitalised with meningococcal disease. John was given prophylaxis,
and returned to the hospital. The rash remained, but he was well. The repeat blood
tests had shown Hb 12.6 g/dl, WBC 9.6 x 10 9/1, platelets 411 x 109 /I, CRP 54 mg/I. On
this third visit, further repetition showed Hb 12.4 x 10 9/1, WBC 9.4 x 109/1, platelets
511 x 109/1, CRP 4 mg/I.
He and his parents are frightened: could it be meningitis?
What do you say?
i. It is likely that John has glandular fever
ii. It is possible that John has meningococcal disease
iii. It is unlikely that John has meningococcal disease
iv. It is unlikely that John has glandular fever
v. It is possible that John has meningitis
vi. The symptomatology is too mild for untreated meningococcal disease
vii. Meningococcal disease always presents acutely
viii. John possibly needs treatment with antibiotics
ii. It is possible that John has meningococcal disease
iv. It is unlikely that John has glandular fever
.0 viii. John possibly needs treatment with antibiotics
C
!!l
())
Repeated clinical examination has not shown meningism. It is very unlikely that John
o·
::I
has meningitis. Meningococcal disease can present as n1eningitis and/ or septicaemia.
Vl
Ill Septicaemia usually presents acutely with rapid onset and fatality. The classic rash is
:::::i petechial and/ or purpuric. However, there is also a subacute form, which may also
c..
have generalized petechial rash and may progress to cause focal infection in the menin
)>
::I ges, joints, heart or eye. The chronic form of n1eningococcal sepsis 1nay have anorexia,
weight loss, fever, arthralgia or arthritis and a non-itchy, blanching, macular skin rash.
())
'""'I
Vl
Erythema nodosum or bacterial endocarditis may occur.
In• its early stages, even the acute form of meningococcal disease, soon to fuhninate,
,-+ may have a n1acular, blanching or even urticaria! rash.
::::r
())
The differential diagnosis of meningococcaemia may be broad. A morbillifonn rash
z
(D q1ay be caused by a drug or other allergy, or viral infections including n1easles. Other
bacterial and viral infections may cause purpura. Henoch-Schonlein disease usually has
"Tl
0 purpura, but may be 1nacular. Idiopathic thrombocytopaenic purpura gives petechiae,
3
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purpura or bruising.
,-+
m Subacute and chronic n1eningococcaemia present additional challenges, with a differ
>< ential diagnosis including many causes of arthritis and fever.
OJ
3 Further tests include blood for culture, PCR and serology. Swab from posterior
pharyngeal v.rall (either orally or per nasally). A scrape of the rash may show
. .
menmgococo.
John's tests showed that he had meningococcaemia. Treated with antibiotics, he suf
fered no ill effects.
120
1. Coeliac disease
2. Crohn's disease
3. Ulcerative colitis �
:::0
4. Cows' milk protein intolerance ()
-0
5. Toddlers' diarrhoea ()
I
6. Cystic fibrosis -0
7. Lactose intolerance ....
Q)
r+
8. Irritable bowel syndrome N
9. Abdominal migraine
10. Haemolytic uraemic syndrome (HUS)
the list above.
a. A-15-year old boy presents with delayed puberty and short stature. Both parents'
height lies on the 75th centile. He looks pale and thin. He recently presented to his
general practitioner with a painful red swelling on his shin which has now resolved.
Examination reveals aphthous ulceration in his mouth, but is otherwise
unremarkable.
b. A 3-year-old has intermittent diarrhoea with stools of varying consistency and
sometimes undigested food particles. His growth is following the 9 th centile. His
mother is concerned and has tried to reduce his intake of dairy produce but his
symptoms have not improved.
c. An 11-month-old infant presents with a history of persistent loose stools and poor
weight gain since breast feeding was discontinued at 9 months. He has had
antibiotics on two occasions from his general practitioner for chest infections. Initial
investigations reveal a mild metabolic alkalosis with hypokalaemia.
121
a. 2. Crohn's disease
,0
C: Crohn's is a chronic granulomatous inflamn1atory disease of the bov.rel involving the
�
o·
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·whole gastrointestinal tract from n10uth to anus. The inflammation is transmural with
skip lesions. Presenting syn1ptoms include abdominal pain, diarrhoea and weight loss,
Vl
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although there may be no abdominal sym.ptoms. Growth failure with delayed bone
:, maturation and delayed puberty can occur. There has been an increase in the incidence
0...
of Crohn's over the last few years.
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b. 5. Toddlers' diarrhoea
'""I
Vl This is a clinical syndrome characterised by chronic diarrhoea often with undigested
-+,
0
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food in the stools of a child who is othervvise well, gaining weight and growing satis
r+ factorily. Bowels may be opened up to six times a day, and stools niay contain nmcus
:::;
CJ) (but no blood). Stools are often looser tavvards the end of the day. Symptoms usually
z
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start between 8 and 20 months of age, and there rnay be a family history of irritable
� bowel syndrome. No treatn1ent other than reassurance is necessary.
,,
0
3 c. 6. Cystic fibrosis
OJ
r+ CF is a nrnltisystem disease and is characterised by the production of very viscous
m nrncus at epithelial surfaces. Inheritance is autoson1al recessive and prevalence is 1: 2000,
X
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with a carrier frequency of 1 : 20. There is a deletion on the long arrn of chromoson1e
3 7, which results in a defect in a transmen1brane regulator protein called the cystic
fibrosis transn1e1nbrane conductance regulator (CFTR). This represents a cAMP medi
ated chloride channel. In the lungs, normal CFTR causes efflux of chloride ions across
apical membranes of the submucosal glands, followed by sodium and vvater. In CF,
there is an inability to secrete chloride, sodium. and water, resulting in thick secretions.
A similar problern occurs in the pancreatic and biliary ducts. However, in the skin,
the function of sweat glands is to absorb chloride from the isotonic sweat, so in CF,
this doesn't happen and there is therefore a high sweat chloride and sodium. (the basis
of the sweat test).
1.22
s:
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fl
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fl
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0)
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N
C
a b
Fig 3.19
A 10-year-old girl complained of pain in her upper left thigh since the age of 7 years,
which had been attributed to growing pains. However, the pain had persisted and
recently got worse requiring analgesia. Plain X-ray (Fig. 3.19.a) showed an abnormality,
which was imaged by MRI (Fig.3.19.b). Physical examination revealed her as having
three large cafe au lait marks which had been present since birth (Fig. 3.19.c). She was
pubertal at Tanner breast stage 4. Whole-body radionucleotide scanning revealed
multiple bony abnormalities which were asymptomatic. Bone biochemistry and
gonadotrophin releasing hormone stimulation tests results are shown:
Table 3.19.1
Ca P04 ALP TRP TmP04' Peak LH Peak FSH Oestradiol

{2.1-2.6} {0.9-1.8} {150-570} {>80%} GFR IU/1 IU/1 (75-1470}
mmol/1 mmol/1 IU/1 {1.4-2.6} pmol/1
2.43 0.92 1406 87% 0.8 10.9 7.2 78
TRP: tubular reabsorption of phosphate; TmP04'GFR: tubular reabsorption of phosphate corrected for glomerular
filtration rate, numbers in brackets indicate normal ranges

i. McCune Albright syndrome
ii. Osteomalacia
iii. Fanconi syndrome
iv. Neurofibromatosis type I
v. Ollier's disease
vi. Osteopetrosis
123
ANSWER TO CASE 3.19
i. McCune Albright syndrome
.0 The likely diagnosis is McCune Albright syndrome. Hmvever, characteristically, MAS
C:
(I) is associated with skin lesions, bony lesions and endocrinopathies.
VI
o·
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The plain X-ray shows a bone cyst in the femur, which is confinned in the MRI scan
::I
VI in the left upper thigh and the skin pigmentation in Figure 3.19 .1 c shovvs coast of
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Maine pigmented cafe au lait spots. The multiple asymptomatic bony abnormalities
Cl. revealed on the radionucleotide scan de1nonstrate polyostotic fibrous dysplasia.
)>
::I The most con11non associated endocrinopathy is gonadotrophin-independent preco
� cious puberty where luteinised follicular cysts within the ovaries function autono
�
V,
mously. Pituitary adenomas capable of secreting excess LH, FSH, GH and/ or prolactin
-h have been reported. Patients may have Cushing's syndrome and hyperthyroidism due
0
"""\ to autonomous nrnltinodular hyperplasia. The syndron1e occurs in incon1plete as ·well
r+
::::r as in expanded forms. Precocious puberty and bone lesions niay occur in the absence
(D
of cutaneous 111anifestations; furthern10re, not all patients have sexual precocity. This
z
(D patient has an early puberty since she is at Tanner breast stage 4 at an age of 10.3
� years. Her GnRH stirnulation tests demonstrate a centrally mediated pubertal response,
-n
0 in keeping with normal centrally mediated puberty.
3
OJ Renal phosphate wasting may occur in MAS, resulting in hypophosphataemic rickets.
r+
m Calcium and phosphate are often normal but alkaline phosphatase and other biochemi
>< cal markers of bone turnover may be elevated as in this case where phosphorus is at
OJ
3 the lmver end of normal range ,vith raised alkaline phospatase and lmv TmP04 when
corrected for GFR. These patients may benefit from. treatment with phosphate sup
plen1ents and a vitamin D analogue. Recently, the bisphosphonate, pa1nidronate, given
i.v. has been used for bone pain.
124
$
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Fig 4.1
What are the three most important signs to elicit during examination of this 16
year-old girl?
i. Trigeminal nerve paraesthesia
ii. Tenderness over temporal region
iii. Involvement of frontalis muscle
iv. Associated herpetic lesions in the external auditory meatus
v. Pupillary constriction
vi. Associated hearing impairment
127
ANSWERS TO CASE 4.1
iii. Involvement of frontalis muscle
iv. Associated herpetic lesions in the external auditory meatus
vi. Associated hearing impairment
This girl has right-sided facial nerve palsy. The differential diagnosis includes Bell's
palsy, Moebius syndrmne and Ramsay-Hunt syndrome.
Q) It is important to establish the following during your examination:
::J
c.. Whether it is an upper or lower motor neurone deficit (Bell's palsy is a lower motor
)> neurone lesion - thus the forehead is involved)
:J
VI Associated herpetic vesicles in the external audit01y meatus (Rarnsay-Hunt)
� Associated VI nerve palsy (possibly Moebius syndrome but usually bilateral)
.,
(D
VI Associated hearing irnpainnent (possible acoustic neuroma)
-+,
.,
0 Can the patient close the eyelids? (indication for methylcellulose eyedrops)
r+
:::y
(D Facial nerve
z
(D In supranuclear paralysis (upper 1notor neurone) only the lower part of the face is
�
.,,
0
involved because of the bilateral upper motor neurone innervation of the forehead. In
infranuclear paralysis (lower motor neurone), both the upper and lower parts of the
3
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face are involved equally, e.g. Bell's palsy.
r+
m
X
Patterns of muscular weakness
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3 Upper 1notor neurone: increased tone, increased reflexes, pyramidal pattern of
weakness (weak extensors in the arm, v,reak flexors in the legs)
• Lower motor neurone: wasting, fasciculation, decreased tone and absent reflexes
128
A full-term infant was delivered by emergency Caesarean section for placental
abruption. Immediately before the Caesarean section, there had been a fetal
bradycardia. At delivery, he was white, bradycardic and made no respiratory effort. He
required bag and mask ventilation for the first 12 min of life following which he started
to gasp and breathe normally. His Apgar scores were 1 at 1 min and 5 at 5 min. The
cord pH was 6.85. After admission to the neonatal unit, he remained lethargic and
hypotonic. The initial arterial blood gas showed the following:
pH 6.95
PC02 2.6 kPa
P0 2 11.3 kPa
HC0 3 14 mmol/1
Lactate 15.4 mmol/1
A cranial ultrasound scan was normal. His condition improved, although he required
oro-gastric tube feeds until 6 days old, following which he started to feed normally by
bottle. At discharge, neurological examination was normal.
a. Which of the following is not an expected complication during the neonatal
period?
i. Hepatic necrosis
ii. Seizures
iii. Renal dysfunction
iv. Hypertension
v. Deranged coagulation
vi. Hyaline membrane disease
b. Which clinical factors suggest a worse prognosis?
i. Hypothermia
ii. Hypertonia
iii. Irritability
iv. Prematurity
v. Severe hypotonia
vi. Seizures
vii. Unconsciousness
129
a. iv. Hypertension
b. v. Severe hypotonia
vi. Seizures
vii. Unconsciousness
This baby has hypoxic-ischaemic encephalopathy (HIE). Con1plications include renal
OJ
failure, hepatic necrosis (elevated liver enzymes), clotting abnormalities and DIC,
:::i hyaline membrane disease, persistent pulmonary hypertension, and myocardial dysfunc
Cl.
tion (hypotension, low cardiac output).
)>
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Clinical assessment of this condition is the n1ost useful way to assess severity and prog
�
(D nosis. Sarnat and Sarnat described the clinical grading of HIE. There are three grades
"""I
Vl of severity recognised.
-+,
0
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Grade I: Irritability, hypotonia, increased arousal, poor feeding initially but improv
r-+ ing by day 2-3. No seizures. Good outcome usual (<2% have severe
::::,
(D handicap).
z
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Grade II: Lethargy, abnormal tone, may be some multi-organ involvement (renal
failure, hepatic impairment, etc.). Seizures. Poor feeding for first week of life.
"Tl Variable outcome.
0
3
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Grade III: Multi-organ involvement, decreased consciousness level or unconscious
ness, severe hypotonia, prolonged and difficult to control seizures. Death or
r-+
m poor outcome very likely (70-80%).
><
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The neurological behaviour during the neonatal period remains the best prognostic
3 marker. This infant had a Sarnat grade II hypoxic ischaemic encephalopathy. Approxi
mately 20% of infants with HIE of this severity will have developmental impairn1ent.
The poor prognostic features in this case are that the first gasp was at 12 min of age,
the infant had seizures, the cord and arterial pH were both low (<7.0) and the lactate
(and base excess) was high. The good prognostic features were that he responded to
anticonvulsants and did not continue to fit, had a norn1al neurological examination
before discharge, and bottle fed within a week of age. The normal cranial ultrasound
scan does not help to guide prognosis. In1aging using CT or MRI may be useful par
ticularly if performed after the first week of life, and EEG has also been shown to
predict outcorne. There are no clinical interventions which have been shown to
in1prove outcome, but there has been recent interest in the use of hypothermia as a
therapeutic manoeuvre.
130
A male infant was born at 38 weeks' gestation, by spontaneous vertex delivery,
weighing 4500 g. You are asked to see the baby in the postnatal ward at 48 h of age
because the mother feels he has a large tongue. On examination he is settled and
sleeping. He has a large and slightly protruding tongue, linear creases on both ear
lobes and an umbilical hernia. Examination of his abdomen reveals 2 cm of liver
palpable but is otherwise normal.
a. What investigation would you carry out first?
1. Ultrasound abdomen
ii. Serum calcium
iii. Echocardiogram
iv. Check patency of oesophagus with nasogastric tube
v. Blood glucose
vi. Examination of palate
b. What condition is the baby at risk of in later life?
i. Leukaemia
ii. Coeliac disease
iii. Wilm's tumour
1v. Diabetes mellitus
v. Eisenmenger's syndrome
vi. Glue ear
vii. Osteoporosis
131
ANSWERS TO CASE 4.3
a. v. Blood glucose
b. iii. Wilm's tumour
This baby has several features which suggest Beckwith-Wiedemann syndron1e: macro
somia, macroglossia, ear lobe creases and an un1bilical hernia.
Congenital hypothyroidism, which could give you macroglossia and un1bilical hernia,
OJ would not result in macrosomia or the characteristic ear lobe creases.
:::!
a.
Beckwith-Wiedernann syndrome is related to an abnormality in the chron10some
)>
::::,
V,
11p15.5 region. Other features include mild n1icrocephaly, hemihypertrophy, neonatal
polycythaemia and cryptorchidism. Omphalocoele/ ex01nphalos or other un1bilical
�
(D
V,
anomalies may be present. Babies n1ay have feeding and associated breathing problerns
-I-, in the neonatal period related to size of tongue.
0
�
r+ Mild-to-moderate mental deficiency present in some cases is related to undiagnosed
:::;
(D and/ or untreated hypoglycaemia that is present in 33-50% of cases. Otherwise, mental
z
(D
function appears to be normal.
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Children with Beckwith-Wiedemann are at risk of developing tmnours, in particular
Wilm's tun10ur, hepatoblastoma, adrenal carcinoma and gonadoblastoma.
3
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3
132
A 10-year-old boy presents with a 3-month history of gradually increasing weakness,
lassitude, dizziness and some abdominal pain. His schoolwork has deteriorated a little.
.,,n
On examination he is found to be hypotensive and collapses on standing. Basic serum (1
biochemistry shows:
.,,
Urea 5 mmol/I :::r:
Creatinine 80 µmol/I Qj
Na 127 mmol/I �
K 5.8 mmol/I N
Ca 2.3 mmol/I
a. What findings on examination may prove helpful?
i. Acanthosis nigrans
ii. Buccal mucosa pigmentation
iii. Ejection systolic murmur
iv. Cataracts
v. Pigmented scars
vi. Eczema
b. What other investigations would you consider?
i. Adrenal antibodies
ii. Glucagon stimulation test
iii. Testosterone
iv. ACTH stimulation test
v. Adrenal USS
vi. CT head
vii. 17-hydroxyprogesterone
viii. Echocardiogram
ix. Karyotype
133
ANSWERS TO CASE 4.4
a. ii. Buccal mucosa pigmentation
v. Pigmented scars
0 c. i. Adrenal antibodies
C
(I)
iv. ACTH stimulation test
�
a· v. Adrenal USS
::i
V)
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The findings of hyponatrae1nia, hyperkalaemia and hypoglycaemia point to a diagnosis
::i of Addison's disease. The finding of hyperpign1entation on examination would be
0.
helpful in making the diagnosis. Such increased pign1entation often has the appearance
)>
::i of a well suntanned skin; freckles and old scars n1ay darken and there is also sometimes
� pigmenting of the buccal mucosa.
�
V) Further investigations should include an ACTH stimulation test, adrenal antibodies (e.g.
-+,
0
'""'I
antiadrenal cytoplasn1ic antibody) are usually raised, and screening for other autoanti
r+ body disorders that may occur with Addison's (e.g. diabetes mellitus and hypoparathy
:::,
(D roidism). In the 1najority of cases Addison's is an autoimmune disorder but very long
z
(D
chain fatty acids should be requested in this boy as there is an association with adre
� noleukodystrophy and he is having difficulties at school. Imaging of the adrenal glands
-n may prove useful in identifying other more rare causes.
0
3
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r+
m
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3
134
A 5-year-old Indian boy acutely developed hemiplegia after 5 days of fever, intermittent
photophobia, neck and backache, and 3 days of irritability, with occasional vomiting.
Previously he was healthy and fully immunised, including BCG. He had not travelled
abroad. Airway, breathing and circulation were normal. GCS was 14, and temperature
was 38.5 °C. His left arm and leg had reduced power, increased reflexes and an
upgoing plantar reflex. He had a left facial nerve palsy. There was no rash. Cefotaxime
and acyclovir were started.
CT head showed no space-occupying lesion, no signs of raised intracranial pressure, but
meningeal enhancement with contrast. In 8 h, his neurological deficits had greatly
improved. After careful consideration, a lumbar puncture was performed.
Blood results were: Hb 11.3 g/dl, WBC 15.6 x 109/1, neutrophils 11.3 x 109 /I, platelets
207 x 109/1, CRP 80 mg/I, Na 128 mmol/I, K 3.4 mmol/I, urea 5.3 mmol/I, creatinine
57 mmol/I, Ca 2.21 mmol/I and glucose 7.8 mmol/1.
CSF results were: glucose <0.6 mmol/I, lactate 10.4 mmol/I, protein 0.95 g/I, WBC
500/mm3 (99% lymphocytes), red blood cells 45/mm3, no organisms seen.
Which of the following is the most likely diagnosis?
i. Viral meningitis
ii. Tuberculosis
iii. Listeria
iv. Cryptococcus
v. Acute bacterial meningitis
135
ANSWER TO CASE 4.5
iii. Listeria
The differential diagnosis includes tuberculosis, listeria, cryptococcus, and acute bacterial
C:
meningitis (which can present with lymphocytic infiltrate). Although viral meningitis
�
(t)
is possible, it is unlikely as the CSF glucose is very low.
,;-
::::i
t..n Following the CSF results, antituberculous chemotherapy (rifampicin, isoniazid and
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::,
pyrazinamide) should be added, and either meropenem or an1picillin to cover listeria.
a.. Steroids (for tuberculous meningitis vvith nerve palsies) and antifungals should be con
)> sidered. Further investigations include:
::::i
For tuberculosis - Ziehl-Nielsen or auramine stain, CXR and tuberculin skin test
For cryptococcus - Indian ink stain and antigen tests
"""I
t..n
- His CSF grew Gram-positive rods (Listeria monocytogenes). Ampicillin and gentamicin
0
"""I were given for synergy.
r+
:::;
ro Listeria, an uncommon pathogen in the general population, is irnportant in pregnancy,
z neonates, the elderly and those immunocon1promised. In the USA, incidence is 7.4
ro
cases per million population: 27% being pregnant women. Seventy per cent of non
,,
0
perinatal infections are in immunocon1promised patients. Lower incidence figures have
3
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been reported in the UK. No impairment of the host defences of this child has been
found. Contaminated food is usually the source. Listeria has been isolated from_ raw
r+
m
meat, dairy products (particularly soft cheeses and unpasteurised milk), vegetables and
><
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:3 The most conm1on manifestation is diarrhoea. Fever, nausea, vonuting and diarrhoea
may resemble gastrointestinal illness. Recently, it has been associated with epidemic
gastroenteritis. Bacteraemia and meningitis are more serious. Listeria has a predilection
for the brain parenchyma, especially the brain stem and the meninges. Mental status
changes are common. Seizures occur in at least 25%. Cranial nerve deficits may be
present. Neck stiffoess is less common. Movement disorders may include tremor, myo
clonus and ataxia. There may be encephalitis, particularly brain stem. Brain abscess
occurs in 10% of CNS infections and has high mortality. Blood cultures are positive
in 60-75% of patients with CNS infections. Listeria demonstrates 'tumbling motility'
in wet mounts of CSF. CSF Gram stain is positive in 50%, and culture in nearly 100%.
Serologic testing is unreliable.
Early-onset neonatal listeriosis has a 20-30% mortality rate. Late-onset neonatal listerio
sis has a 0-20% mortality rate. Mortality in older children is less than 10%. Hydro
cephalus, mental retardation and other CNS sequelae have been reported in survivors
of Listeria meningitis.
136
A 3-week-old ex-29-week infant remained in the neonatal unit nursery for nasogastric
feeding, monitoring of apnoea and bradycardia, and treatment of gastro-oesophageal
reflux with ranitidine and cisapride. Erythromycin was commenced for what was
thought to be a mild atypical pneumonia. Twelve hours later this infant had an
unexpected cardiac arrest just before a feed and died.
Echocardiogram during attempted resuscitation showed ventricular fibrillation. Post
mortem showed no milk in the trachea.
A resting ECG taken the previous week had shown HR 150/minute; RR interval = 0.4 s;
QT= 0.32 s.
a. What abnormality is demonstrated by the ECG?
1. Tachycardia
1i. Short RR
iii. Long QT
Iv. Short QT
v. Sinus arrhythmia
What are the likely factors contributing to the fatal episode?
i. Prematurity
ii. Cisapride treatment
iii. Nasogastric feeding
iv. Erythromycin therapy
v. Associated apnoea
137
ANSWERS TO CASE 4.6
a. iii. Long QT
b. ii. Cisapride treatment
,0
C: iv. Erythromycin therapy
,,.
(1)
V)
r+ These results show prolonged QT syndrome. The corrected QT interval is calculated
::,
by
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CL
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V)
The upper normal limit of QTc: 0.45 s for boys; 0.46 s for girls. In this case the QTc
� is O .51 s.
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The QT prolongation is probably secondary to cisapride and exacerbated by erythro
-h
0 mycin. Prolonged QT can also be exacerbated by hypocalcaen1ia.
�
r+
:::; Cisapride is no longer used for the routine treatment of reflux, although it can be
(D
z prescribed in rare circumstances, when a resting ECG nmst be performed first. Other
(D drugs which can precipitate prolongation of the QT include:
� macrolides
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0 antihistamines
3
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salbutamol
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m
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3
138
Fig 4.7
This term newborn baby developed respiratory difficulties shortly after birth. There were
diminished air sounds bilaterally but particularly on the left side. The apex beat was
located on the right, there were no murmurs and the pulses were all easily palpable.
The abdominal examination was normal.
a. What is the diagnosis?
SELECT THE BEST ANSWER
i. CCAML
ii. Congenital diaphragmatic hernia
iii. Congenital pneumonia
iv. Bilateral pneumothoraces
v. Staphylococcal pneumatocoeles
vi. Pulmonary interstitial emphysema
b. What would be your immediate management?
1. Check blood gas and ventilate if necessary
i 1. Book emergency theatre
iii. Paralyse
iv. Urgent echo to exclude associated cardiac lesion
v. Intubate and ventilate
vi. Sedate
139
ANSWERS TO CASE 4.7
a. ii. Congenital diaphragmatic hernia
b. iii. Paralyse
v. Intubate and ventilate
vi. Sedate
The CXR shows bowel gas shadowing, most visible at the mediastinmn and the
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left chest. This is a diaphragmatic hernia. A scaphoid abdon1en is not necessarily a
::::l feature.
a..
)> A number of different diaphragmatic hernias have been described. Retrosternal (Mor
::::l
gagni) and posterolateral (Bochdalek) are the two classical defects. At 8 weeks' gestation
�
ro the pleuroperitoneal canals close, separating the abdominal and thoracic cavities. Failure
""'I
II' of these canals to close may be just one cause. Other mechanisms, such as disruption
-
0
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of the developing thoracic n1.esenchyme, have been postulated.
,-+
::::; Sedation, paralysis, ventilation and nasogastric drainage are generally the most important
ro
initial management steps. In utero reduction is being attempted in certain centres.
z
ro
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140
A 14-month-old girl was brought into accident and emergency (A&E) by ambulance at
0600 h one morning, fitting. Her parents gave a history that she had been well until s::
:;7J
the previous morning when she had developed a coryzal illness. She had been seen by (")
the GP, who noted that she was pyrexial and diagnosed a viral illness. She had fed -0
(")
poorly that day, had been drowsy and had been vomiting. She had gone to bed :c
without eating, although she had tolerated some clear fluid. She slept in her parents' -0
OJ
bed that night and they were woken by her fitting. Her parents were healthy and ;:i
unrelated. There was no family history of note; she was their first child. N
On arrival in A&E, she was still fitting. She had a temperature of 38.5° C but no rash.
She had hepatomegaly. Her initial investigations showed:
Na 129 mmol/I K 4.4 mmol/I
Urea 3.7 mmol/I Creatinine 55 µmol/I
Glucose 0.9 mmol/I
AST 256 u/I ALP 350 u/I
Bilirubin 30 µmol/I Ammonia 88 µmol/I (10-47)
Urine dipstick negative, no ketones
a. What would your initial management be?
i 100% oxygen
ii. Phenobarbitone
iii. i.v. glucose infusion 6-8 mg/kg/min
iv. Sodium benzoate
v. Bolus of iv glucose
vi. 0.9% NaCl infusion
vii. i.v. lorazepam
i. Hyponatraemic seizures
ii. Meningococcaemia
iii. Diabetes insipidus
iv. Medium-chain acyl-CoA dehydrogenase deficiency
141
ANSWERS TO CASE
a. i. 100% oxygen
v. Bolus of i.v. dextrose
D vii. i.v. lorazepam
C
ro b. iv. Medium chain acyl-CoA dehydrogenase (MCAD) deficiency
�
o·
::l
Initial management involves care of the ainvay and breathing, and administering 100(¼)
V\
OJ OJ\.1gen. Appropriate blood specin1ens should be taken and a bolus of i.v. 10% glucose
::l 2-5 ml/kg given followed by a continuous infusion providing 6-8 mg/kg/min glucose.
a.
Seizures should be treated according to the status epilepticus protocol. The glucose
)>
::l
V\
should be rechecked after 3-4 min and a repeat glucose bolus given if still <4 mmol/1.
ro Bloods should be obtained at the tin1e of hypoglycaemia ,vithout delaying treatn1ent.
.....
V\ Samples to be sent immediately should include: glucose, lactate, ammonia, U&Es, LFT,
-+,
0
..... FBC, CRP, blood cultures and blood gas. Samples should be immediately frozen and
,-+ stored for: plasma an1ino acids, cortisol, GH, ACTH, ketone bodies, free fatty acids,
::r
(J) mediun1 chain fatty acids, carnitine, uric acid, triglycerides. Blood spots should be sent
z for acylcarnitine. The first urine voided (catheterise if necessary) is vital, and should be
ro
sent for ketones, reducing substances, organic and an1ino acids and toxicology.
'Tl
0 There is no typical presentation of MCAD deficiency, but children often present
3OJ bet,veen 3 and 15 months of age with an episode of vorniting and lethargy following
,-+ a period of fasting. There may be an associated minor illness. In 20% of families, there
m n1ay be a history of unexplained sibling deaths. The initial laboratory findings are of
><
OJ hypoglycaen1ia (although normal blood glucose levels have been seen), mild elevation
3 of ammonia (50-100 µmol/1), mild elevation of transaminases, and hypoketosis.
142
A 10-year-old boy presents with a history of nervous twitches from the age of 4 years,
which vary over time and fluctuate in severity. Mouth opening, eye blinking, grimacing
and arching of his neck have been witnessed. He compulsively clears his throat and
s:
Al
(')
makes grunting noises. The problems are worse when he is under stress. His behaviour ".U
(")
in school is problematic but parental management seems appropriate. He is attention I
seeking and impulsive, cannot wait his turn and shouts out in class. He is fidgety and -0
frequently gets out of his seat. His concentration is poor in class, yet he performs well ....
OJ
r+
when working alone. Background knowledge and verbal performance are good but his N
educational progress has slowed. He is described as moody but well behaved at home.
He enjoys drawing and is meticulous. His parents are concerned about his social
adjustment. Birth and medical history are unremarkable. The parents are healthy and
did not experience similar difficulties. A distant relative has epilepsy and a grandparent
has Parkinson's disease. Examination including neurological assessment is normal.
Involuntary twitches are witnessed, although there is no dystonia or choreiform
movement. An EEG has been reported to be normal with movement artefact.
i. Tourette's syndrome
ii. Accidental ingestion
iii. Parkinsonism
v. Obsessive-compulsive disorder
vi. Post-streptococcal neuropsychiatric disorder
vii. Carbon monoxide encephalopathy
143
ANSWER TO CASE 4 •.9
i. Tourette's syndrome (TS)
Tourette's syndrome is a neuropsychiatric disorder of childhood onset. Diagnostic cri
C:
teria include multiple (two or n1ore) motor tics, at least one vocal tic, and duration of
�
(D
symptoms longer than 1 year. Prevalence is -1-3% in children, higher in boys. Peak
o·
::::::;
onset is at 5-7 years. Motor or vocal tics may be simple (e.g. shrugs, grim.aces, barks
VI
Q)
and grunts) or complex (e.g. smelling, touching, copropraxia, coprolalia and echolalia).
:, Flamboyant phenomena are rare. Tourette's syndrome has also been reported secondary
0..
to lamotrogine medication, in citrullinaemia, perinatal asphyxia, Down's syndrome and
)>
::::::;
VI
autism.
Differential diagnoses include:
�
VI basal ganglia disorders, e.g. Wilson's disease, carbon monoxide encephalopathy,
-
0
� post-encephalitic parkinsonism and tardive dyskinesia (unlikely in this case)
r+ accidental ingestion or deliberate poisoning (acute presentation)
::::r
<D • PANDAS (Paediatric autoimmune neuropsychiatric disorders associated with strep
z
<D
tococcal infection) - infection-triggered, autoimmune subtype of paediatric obsessive
compulsive disorder and Tourette's syndrome - the working criteria include pres
"Tl ence of OCD and/or tic disorder, prepubertal onset, acute presentation, episodic
0
3
Q)
syrnptom severity, recent group A beta-haemolytic streptococcal infection and neu
rological abnormalities
r+
m
><
If the presentation is typical and careful neurological evaluation is normal, no further
OJ investigations are indicated. Investigations may be indicated in atypical cases. The EEG
3 is non-specific in Tourette's syndrome. Radiological investigations are unlikely to be
informative.
Associated conditions include OCD, ADD/H, specific learning problems, visuomotor
difficulties and migraine (more prevalent in Tourette's syndrome). Comorbid disorders
are often 1nore detrimental than the tics. The ADD/H child may be perceived as
deliberately naughty or disruptive. Obsessional behaviour may bring the child into
conflict with others. The child may experience low self-esteem, anxiety and depression,
teasing and bullying. School difficulties might therefore be related to educational prob
lems, psychopathology, use of tic-suppressing medication or the direct consequences
of having a stigmatising condition.
The goal of management is to plan individualised therapy to deal with the n1ajor causes
of distress, con1orbid conditions and complications. The farn.ily and those in the social
and educational sphere need information. Specialist involvement may be required.
Medication may be used to reduce tics, control obsessive-compulsive behaviour or
attention problems, or to treat arn,;:iety and depression. Drugs that suppress tics block
dopamine and noradrenaline receptors, e.g. haloperidol, pimozide and sulpiride. Ace
tylcholine-blocking or dopamine-releasing agents may be used for ADD/H, e.g. clo
nidine and methylphenidate (may exacerbate tics). Medication that blocks serotonin
reuptake may help OCD and depression, e.g. tricyclic antidepressants and fluoxetine.
No medication is ideal.
144
s;;
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n
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I
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N
Fig 4.10
A 9-year old girl with known Von Willebrand's disease (VWD) presented with a
3-month history of right thigh and knee pain. There was no history of trauma. Other
than VWD, there was no significant past medical history. On examination she was well.
There was no fever and no rash. Systemic examination was entirely normal. On
examination of her right leg, there were no signs of bruising or erythema. There was
no swelling of any joints and she had a normal examination of her knee and ankle
joints. On examination of her hip, external rotation was limited by pain but was
otherwise normal. X-ray examination of her hips revealed a transverse fracture of the
femoral shaft just below the level of the lesser trochanter.
a. What are the possible diagnoses?
i. Osteogenesis imperfecta
ii. Primary bone tumour
iii. Juvenile rheumatoid arthritis
iv. Fibrous dysplasia
v. Slipped upper femoral epiphysis
b. What investigations would you like to do?
i. cxFP, HCG, CEA
ii. CXR
iii. Autoimmune screen
iv. Fibroblast culture
V. DEXA scan
145
TO 4.10
a. ii. Primary bone tumour
iv. Fibrous dysplasia
C:
b. i. cxFP, HCG, CEA
(0
ii. CXR
�
o·:::::i The 1nost con1mon reason for a pathological fracture in this age group is an isolated
Vl
0,
area of fibrous dysplasia, as in this case. It comn1only presents in mid to late childhood.
:::::i The areas of fibrous dysplasia are benign and n1ay be isolated or multiple (polyostotic).
a.
Polyostotic fibrous dysplasia associated with skin hyperpigmentation and endocrine
}>
:::::i dysfunction (commonly precocious puberty) is known as Albright's syndrome.
(0 Primary malignancies may present with a pathological fracture, e.g. Ewing's sarc01na.
.....
Vl Metastases from a distant primary malignancy (e.g. neuroblaston1a, kidney, thyroid)
-+,
0
.....
should also be considered. Chronic bone infection is also a differential diagnosis.
,-+ Appearances on X-ray are a helpful guide to diagnosis that may be further aided by
::,
(0 MRI.
z
(0 Investigations which may be necessary include FBC, U&E, LFT, CRP, Ca, and P0 4 .
.,,
0
Also aFP, HCG, CEA (as tumour markers), a CXR (to exclude mediastinal tun1our),
an abdon1inal USS (to look for evidence of neuroblastoma), urine HVA and VMA, an
3
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MRI of the lesion and a bone scan.
,-+
m
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3
146
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Fig 4.11
A pregnant woman was admitted at 32 weeks' gestation feeling unwell and vomiting.
Her antenatal course had been uneventful prior to this admission, and the 20-week
anomaly scan was reported as normal. Initial assessment revealed a fetal bradycardia,
and the baby was delivered by emergency Caesarean section. At birth, the baby was
blue with poor respiratory effort and a bradycardia of 60-70 bpm. She required
intubation and ventilation which led to an improvement in colour but the heart rate
remained below 100 bpm. On admission to the neonatal unit, a CXR revealed marked
hyaline membrane disease, and an ECG was obtained.
a. What is the ECG abnormality?
i. Short PR interval
ii. Second degree heart block
iii. Delayed repolarisation syndrome
iv. Congenital complete heart block
v. Prolonged QT interval
b. Which is the inotrope of choice in unstable babies with this condition?
i. Dopamine
ii. Noradrenaline
iii. lsoprenaline
iv. Atropine
v. Flecainide
c. Which of the following maternal conditions can predispose to this
condition?
i. Parvovirus infection
ii. Ehlers-Danlos syndrome
iii. Sjogren's syndrome
iv. Polyarteritis nodosa
147
a. iv. Congenital complete heart block (CCHB)
b. iii. lsoprenaline
D
C c. iii. Sjogren's syndrome
(I)
� The ECG shows congenital CHB ·which can be associated with a n1.aternal history of
5· systemic lupus erythen1atosus (SLE) or Sjogren's syndrome. The prevalence of con
:::l
V'l
OJ
genital CHB in newborns of prospectively followed-up women already kn0vvn to be
:::l anti-Ro/SSA positive and with known connective tissue disease is 2%. This finding is
0..
useful ·with regard to preconception counselling. The risk of delivering an infant \Vith
)>
:::l
V'l
congenital CHB may be higher in mothers with Sjogren's syndrome than in those with
� SLE. Additional electrocardiographic abnormalities such as sinus bradycardia and pro
""'
(I)
V'l
longation of the QT interval may be present in their children.
-h
Q An echocardiogram was carried out to exclude congenital heart disease. This baby had
...+ a large secundum atrial septal defect with bidirectional flow. The heart sh0vved biven
::;
(I) tricular hypertrophy, presumably in response to longstanding heart block.
z
(I) Pacing is the definitive management. The management of the preterm fetus with hy
� drops caused by congenital CHB is difficult, with associated morbidity and mortality.
71
0
3
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...+
m
X
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148
A 7-year-old boy presented with an 18-month history of poor growth and failure to
gain weight. His appetite was poor and he was lethargic such that he had to be carried �
:;:u
home from school. There was no significant past medical history. On examination, he (i
was pale and subdued. His weight and height were on the 0.4th percentile. He had a '"O
(i
heart rate of 104/minute and a blood pressure of 128/65. There was a systolic murmur :::c
audible all over the praecordium. '"O
QJ
;:l.
Initial investigation showed: N
Hb 4.5 g/dl
Na 141 mmol/I
K 4.4 mmol/I
Urea 80 mmol/I
Total Ca 1.23 mmol/I
Phosphate 3.19 mmol/I
PTH 248 pmol/I (0-7.3)
Urinalysis blood +, protein +
A working diagnosis of end-stage renal failure was made.
a. What non-haematological investigations would you like to perform?
i. Echocardiography
ii Wrist X-ray
iii. Chest X-ray
Iv. Bone marrow aspirate
v. Renal ultrasound scan
vI. 24 hour urinary protein collection
vii. Parathyroid isotope scan
What are the effects of this condition which need to be addressed in the
long-term management of this child?
,. Risk of malignancy
:. Retinal degeneration
Nutrition and growth
, Development of neuropathy
1. Metabolic bone disease
vi. Blood pressure
vii. Psychosis
149
ANSWER TO CASE 4.12
a. i. Echocardiography
ii. Wrist X-ray
t:)
C: v. Renal ultrasound scan
(I)
Vl b. iii. Nutrition and growth
o·
,-+
v. Metabolic bone disease
::,
Vl vi. Blood pressure
ru
::, The \Vorking diagnosis here is end-stage renal failure. This little boy has a GFR of less
Q..
than 10 ml/min/1.73 nl and requires renal replacen1ent therapy, i.e. dialysis. GFR =
)>
::, (height in cm X 40) /creatinine (µmol/1).
� Investigations that need to be perforn1ed include a renal ultrasound scan to help estab
�
Vl
lish the cause of the renal failure, an echocardiogram to determine the cause of the
-h
0
""""i
murmur, and the effect of the blood pressure, and a wrist X-ray should be done to
,-+ confirm bone age and look for osteodystrophy.
::,
(I)
The long-tern, management of this child includes careful fluid and electrolyte balance,
z
(I) maximising nutrition and growth, treating anaemia and metabolic bone disease, close
:;§:
,,
0
observation of the blood pressure and psychological therapy.
3
ru
,-+
m
><
ru
150
A 5-year old girl presented for the third time in a year with peri-anal itching,
particularly at night. A diagnosis of threadworm has been made by her GP in the past, �
and her mother reports having treated it with piperazine, following which her ::::0
(')
,::,
symptoms resolved on each occasion.
(')
What is the likely cause for the child's illness? :::c
,::,
OJ
SELECT ONE ANSWER ONLY �
i. Ascaris !umbricoides N
ii. Ancylostoma duodenale
iii. Sarcoptes scabiei
iv. Wuchereria bancrofti
v. Enterobius vermicu!aris
vi. Ancylostoma braziliense
151
TO CASIE 4.13
v. Enterobius vermicularis
This girl has recurrent Enterobius 1Jennicularis infection, also known as threadworm or
pinworm. Reinfection, and autoinfection (on the child's fingers following peri-anal
scratching at night) are common.
Piperazine can be given as 2 doses 2 weeks apart, and the second dose may be rnissed,
thus encouraging reinfection. Mebendazole or albendazole as a single dose is the first
::J
0,
a.. line treatn1ent. Recurrence despite adequate treatn1ent is con1mon.

)>
::J Confirmation of the diagnosis can be made by the 'Sellotape' test, ideally taken in the
n1orning before washing. The adhesive tape is applied to the peri-anal skin, where
""'I
V,
the eggs are laid, and applied to a slide to facilitate transport for examination under
- the rnicroscope. It is possible to see the eggs using a magnifying glass oneself The
0
""'I worms lay their eggs at night, and they may son1etimes be seen on the peri-anal area
r+
::::; at this time.
(I)
z
(I)
Threadworm may be carried by other n1embers of the household, and treatment of all
family members with a single dose of albendazole or mebendazole in this case would
.,,
0
be indicated. Mebendazole is not reconm1-ended for children under 2 years, and 2 doses
3
CJ
of piperazine 2 weeks apart is an alternative treatment. Finger nails should be kept
short (to prevent eggs being trapped under the nail), and tight undervvear at night may
r+
m help prevent reinfection.
><
CJ
Complications are uncommon as tissue invasion does not occur. In girls, a vulvo
3 vaginitis is recognised, and may cause a vaginal discharge. Iron deficiency anaemia is
not a complication, and if present is likely to be due to dietary or other causes.
Although helminthiasis is often associated with eosinophilia, this is infrequently found
in enterobius infections. Helminth infections have been associated with a reduced
incidence of allergic diseases such as asthma.
No other investigations are necessary.
152
s:
::::0
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N
Fig 4.14
A woman expecting her first baby arrived at the delivery suite in established labour. Her
temperature, pulse and blood pressure were within normal limits. The admission CTG
was satisfactory, fetal movements were present and her membranes were intact. The
following CTG was performed 4 h into the labour. The maternal pulse was 112 bpm
and temperature 37 .8 ° C.
a. Identify the principal features of this trace?
SELECT.THE THREE BEST ANSWERS
i. Fetal bradycardia
ii. Normal beat-to-beat variability
iii. Type I decelerations
iv. Late decelerations
v. Flat trace
vi. Fetal tachycardia
vii. Reduced variability
b. Suggest reasons for a fetal tachycardia?
SELECT THE FIVE BEST ANSWERS
i. Maternal tachycardia
ii. Fetal infection and pyrexia
iii. Maternal infection
iv. Maternal systemic lupus erythematosus (SLE)
v. Preterm gestation
vi. Post dates
vii. Fetal cardiac anomaly
viii. Maternal labetolol therapy
ix. Developing fetal hypoxia
153
ANSWERS TO 4.14
a. iv. Late decelerations
vi. Fetal tachycardia
t:) vii. Reduced variability
c:·
(t)
b. ii. Fetal infection and pyrexia
�
o· iii. Maternal infection
:::, v. Preterm gestation
VI
0, vii. Fetal cardiac anomaly
:::,
0. ix. Developing fetal hypoxia
)>
:::,
VI
Fetal tachycardia is a baseline fetal heart rate > 150 bpm. The fetal heart rate in this
CTG is around 170-180 bpm.. There is also reduced variability; normally the fetal heart
(t)
""'I
VI
rate varies over a minute between 10 to 25 bpm. When the variability is reduced, the
-h rate varies between 6 and 10 bpm.. A reduction in this variation is called a loss of
0
""'I baseline variability, and is associated with fetal hypoxia. Late decelerations are present
,-+
:,- on this CTG; these occur after the onset of the contraction. The greater the tim.e lag
ct>
after the onset of the contraction, the more sinister the trace.
z
(t)
Fetal tachycardia can be associated with any of the following: preterm gestation, devel
"Tl oping fetal hypoxia, maternal anxiety and maternal pain, maternal dehydration, fetal
0
3
0,
activity, fetal infection and pyrexia, maternal infection and fetal cardiac anomaly.
,-+ Management of this case involves assessing the maternal condition and treating with
m
X
i.v. antibiotics for presumed infection. A vaginal examination with artificial rupture of
0, the membrances should be petformed and the colour of the liquor assessed. Fetal blood
3 sampling is useful to measure pH.
Close monitoring of the CTG and maternal progress is mandatory. The baby should
be delivered immediately if fetal blood sampling shows a pH of <7.20 and the paedia
trician should be present at delivery.
154
A 10-day-old male infant presented to the A&E department with a history of being
found lifeless and floppy in his cot by his mother. On arrival at A&E, he was found to
be apnoeic and bradycardic, with a capillary refill time of 6 s. He was intubated and
s:
n
fully resuscitated. Subsequent examination found the infant to be apyrexial and "ti
n
hypotonic, with widespread skin mottling but no other systemic abnormality. He I
subsequently had brief generalised seizures and was loaded with phenobarbitone. On "ti
QJ
making further enquiries into the history, it was noted that there had been a history of ::l
poor feeding for 24 h before presentation. The baby had been born at term in good N
condition and had been fully breast fed.
While he was being ventilated on the paediatric intensive therapy unit, it was noted
that the baby had a mild persistent metabolic acidosis, and he continued to have
seizures. He was extensively investigated.
Results included a raised valine level of 2900 µmol/I (normal 100-400 µmol/I), a leucine
level of 2920 µmol/I (normal being 100-400 µmol/I) and an ammonia concentration of
142 µmol/I (normal 10-40 µmol/I).
i. Pompe disease
ii. Maple syrup urine disease
iii. OTC deficiency
iv. Methylmalonic acidaemia
v. GM1-gangliosidosis
vi. Galactosaemia
b. What is the most likely cause of the seizures?
i. Associated hypoglycaemia
ii. Hypocalcaemia
iii. Raised leucine
iv. Thiamine deficency
v. Raised valine
vi. Hyperammonaemia
155•,
a. ii. Maple syrup urine disease
b. iii. Raised leucine
.0
C With the initial history given, the three main differential diagnoses which nmst be
(I)
� considered are: (1) Neonatal sepsis. (2) Inborn error of n1etabolism. (3) Subdural
o· haemorrhage.
::J
Vl
OJ Investigations that should be performed include:
::J
0.. FBC and differential
)> blood glucose
::J
U&Es
� LFTs
�
Calcium, phosphate and magnesium_
-
0 blood gases
.,
r+ full septic screen including CSF culture
::J"
(I) CXR
z
(I)
cranial ultrasound
CT head
.,
0 The diagnosis here is maple syrup unne disease.
3
OJ The seizures are caused by the very high levels of leucine and the ketoacids that result.
r+
m The high blood level of leucine needs to be urgently lowered by haemodialysis.
>< Catabolism_ must be inhibited and anabolism stinmlated by giving high concentrations
OJ
3 of i.v. glucose in addition to an infusion of low-dose insulin. Lifelong managen1ent
includes restriction of natural protein and supplementation with amino acids, vitamins
and minerals, and there needs to be regular follow-up in a specialist centre. Leucine,
isoleucine and valine (as essential amino acids) need to be included in sn1all an10unts
in the diet.
Maple syrup unne disease is an autoson1al recessive disorder caused by a deficiency
of branched chain keto acid dehydrogenase. This results in the accmnulation of
a-ketoacids (2-oxo-isocaproate, 2-oxo-3methylvaleric acid and 2-oxo-isovalerate) as
well as the branched chain amino acids from which they are derived - leucine,
isoleucine and valine, respectively. The odour of maple syrup, due to 2-oxo-3-
methylvaleric acid, is detected in the urine, sweat and saliva. A urine spot test with
2,4-dinitrophenylhydrazine indicates the presence of ketoacids. The disease is very rare
(1 in 185 000). It presents mainly in the newborn period with an acute encephalopathy
in the forrn of lethargy, vomiting, poor feeding, hyper- or hypotonia, fits and coma.
A significant metabolic acidosis or hypoglycaemia is not ahvays present. The con1bina
tion of a progressive encephalopathy with an absence of significant acidosis, hypogly
caemia or hyperammonaen1ia suggests the diagnosis. There is a n1arked increase of
valine, leucine and isoleucine concentrations in the plasn1a. Patients with si�1ificant
encephalopathy require full intensive care. An en1ergency regimen needs to be devised
for parents to use in the event of an intercurrent illness when there is a serious risk of
n1etabolic decon1pensation.
Patients should be n10nitored by urine testing with dinitrophenylhydrazine. Urine levels
correlate with plasma levels. Mortality from the classic form is up to 20%, death usually
being associated with encephalopathic episodes and cerebral oeden1a. Those surviving
an episode often have high morbidity with significant learning difficulties and spastic
diplegia.
156
A 1-year-old boy was referred to the hospital by his GP with a short history of polyuria
and 'drinking the bathwater'. His mother also suffered with similar symptoms and
received treatment for this. On examination, the child appeared very well apart from a
sticky left eye. Initial results showed:
Na 154 mmol/I
K 3.9 mmol/I
Bicarbonate 27 mmol/I
Urea 2.1 mmol/I
Creatinine 25 mmol/I
Glucose 4 mmol/I
Osmolality 309 mOsm/kg/'
Urine osmolality 283 mOsm/kg ·
What are the most likely diagnoses?
ii. Renal tubular acidosis type 1
iii. Renal tubular acidosis type 2
iv. Hypernatraemic dehydration
v. Water overload
vi. Central diabetes insipidus
vii. Nephrogenic diabetes insipidus
viii. Excess salt ingestion
ix. Bartter syndrome
x. Psychogenic polydipsia
157
vi. Central diabetes insipidus
vii. Nephrogenic diabetes insipidus
.0
C
Confirmation (and to distinguish between the two possible diagnoses) is made with a
�
(I)
water deprivation test with desmopressin.
o·
:::,
VI Central diabetes insipidus may be inherited as an autosomal dominant or autosomal
!lJ recessive disease, The boy's presenting symptoms are consistent with diabetes insipidus,
:::,
Cl. diabetes mellitus and psychogenic polydipsia. However, in compulsive water drinking,
)> serum Na (and osmolality) is usually normal or low. Diabetes 1nellitus in this situation
:::,
VI is ruled out by the nonnal serum glucose. Central and nephrogenic diabetes insipidus
(I) can only be distinguished by a water deprivation test followed by desmopressin injec
""'I
VI tion. In the former, the osmolality of urine shows a striking increase after DDAVP,
-+,
0
""'I
whereas in nephrogenic diabetes insipidus, the urine remains dilute. Central diabetes
,+ insipidus is usually an acquired rather than an inherited condition. In our child, the
:,
(I) disease followed an autosomal dominant pattern with several members of the mother's
z family being similarly affected. Occasionally, it may form part of the autosomal recessive
(I)
Wolfram syndrome (DIDMOAD) when it is associated with diabetes mellitus, optic
,,
0
atrophy and deafness.
3 Primary nephrogenic diabetes insipidus is usually inherited as an X-linked recessive

Q)
,+ disease where male infants present with dramatic polyuria and polydipsia. Females with
m the defect have milder symptoms that may not be detected until later life.
X
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158:
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Fig 4.17
A 7-year-old boy was admitted because of increasing lethargy and tiredness over 7
days. Over the last 12 h, he had been refusing food, vomiting and experiencing
headache. Three weeks before, he had had a cold, conjunctivitis and otitis media, and
that was treated with a course of amoxycillin. Immediately following his admission, he
had a generalised seizure lasting 3-4 min. Fundal examination shows bilateral
papilloedema. A contrast CT scan of brain is shown.
i. Astrocytoma
ii. Demyelinating disease
iii. Brain abscess
iv. Benign intracranial hypertension
v. Subacute sclerosing panencephalitis
vi. Tuberculous meningitis
159
ANSWER TO CASE 4.17
iii. Brain abscess
,0 The CT scan shows a large low attenuation area over the right frontal cortex, with a
C
thin, enhanced ring shadow. These findings, in conjunction vvith the history, are most
;,;- consistent ,vith a diagnosis of a brain abscess.
:,
VI Management involves urgent transfer to paediatric intensive care unit after stabilising,
Ql with urgent neurosurgical referral. He should be treated with i.v. broad-spectrum
:,
0.. antibiotics (ceftazidime + flucloxacillin + metronidazole); i.v. dexamethasone will help
)> reduce oederna and anticonvulsants are needed to control and prevent further seizures.
:,
Fluids should be used judiciously and electrolytes need close monitoring.
�
� Brain abscess usually presents with headache, vomiting, lethargy, fever and fits. Papil
--+, loedema is c01111non and there may be focal neurological signs. Common predisposing
0
.., factors are otitis media, mastoiditis, sinusitis and underlying cyanotic congenital heart
r+
::r disease, but it may occur without any predisposing factors. The organisms most fre
ro quently isolated are microaerophillic streptococci and staphylococcus aureus. Mixed
z
ro organisms may be involved. Neurosurgical referral is urgently needed for drainage of
pus to relieve mass effect and also to identify the organism involved. Pending culture,
.,,
0 broad-spectrum i.v. antibiotics should be given and these may have to be continued
3
OJ
for several weeks. Neurosurgical intervention depends upon location and stage of
r+ abscess, response to antibiotic therapy and clinical condition. Multiple small abscesses
m require aggressive n1edical treatment. A single and encapsulated abscess may need total
><
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excision. Mortality varies between 11 and 15%. Permanent neurological deficits vary
3 between 45 and 65%.
160
A 3-year-old boy presented to A&E with an 8 h history of pain in his hands and feet,
and 1 h of not moving them and not walking. He had been lethargic the previous day, �
::0
febrile overnight, and vomited once. Three days before, he had returned from 6 weeks (')
in India, where he had had several weeks of diarrhoea. His diet included dairy products, "'O
(')
meat and vegetables. :c
"'O
°
His temperature was 38 C. He was alert with no meningism. His wrists and fingers OJ
;::i
were flexed. The rest of his examination was normal. His growth parameters were N
normal. Investigation showed: Hb 9.1 g/dl, WBC 15.6 x 109/1, neutrophils 12.0 x 109/1,
platelets 350 x 109/I, CRP 46 mg/I, Na 139 mmol/I, K 4.0 mmol/I, creatinine 50 µmol/I,
urea 2.8 mmol/I, Ca (total) 1.58 mmol/I, phosphate 1.53 mmol/I, albumin 40 g/I, Mg
0.18 mmol/I.
What was the cause of his paralysis?
i. Guillain-Barre syndrome
ii. Poliomyelitis
iii. Tetanus
iv. Hypomagnesaemia
v. Hypocalcaemia
vi. Paratyphoid
161
ANSWER TO CASE 4.18
iv. Hypomagnesaemia
,0 This boy's tetany is caused by hypomagnesaemia. Second to potassium, magnesium is
C:
(I) the most important intracellular cation. Half is in bone and almost all the rest is in the
� cells of the soft tissues. Less than 1% is in the extracellular fluid. Hypomagnesaemia
o· almost always indicates total body depletion. A child's daily requirement is 0.5-
::i
VI
OJ
1.0 mmol/kg per 24 h. The usual cause of deficiency is increased intestinal loss (mal
::i absorption or fistulae) with or without a reduced dietary intake. In this patient, the
a..
cause was believed to be the prolonged diarrhoea. Occasionally, an increase in urinary
)>
::i excretion (either intrinsic renal tubular disorders or diuretic usage) may result in defi
�
(I)
ciency. Other causes are cirrhosis and chronic mineralocorticoid excess. The normal
""'I
VI
range for plasma magnesium in infants is 0.6-0.9 mmol/1, and in older children and
- adults, 0.75-1.0 rnmol/1. Since magnesium is required for both parathyroid horn10ne
0
""'I secretion and its action on target tissues, magnesium deficiency can cause hypocalcae
,-+
:::r mia, features of both hypoparathyroidism and pseudohypoparathyroidism, and render
(I)
patients insensitive to the treatment of hypocalcaemia with vitamin D or calcium. Both
z
(I) hypophosphataemia and hypokalaemia n1.ay also be present, but all these abnormalities
�
.,.,
0
usually respond to magnesium.
3
OJ
Treatment involves calcium and magnesium replacement; initially i.v., then orally.
,-+
m
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3
162
A 3-week-old infant presents with increasing jaundice, abdominal distension, a 3 cm
palpable liver and a palpable spleen tip. She is noted to have several small
haemangiomas over her body. Her stools are variably pale and her urine dark. She has
mild clinical anaemia with a moderate tachycardia at rest.
Her LFTs are as follows:
Bilirubin 185 µmol/L (Conjugated fraction 94 µmol/L)
ALT 58 U/L ALP 785 U/L
AST 74 U/L Albumin 40 g/L
GGT 403 U/L
i. Neuroblastoma iv. Gilbert's syndrome
ii. Biliary atresia v. Hepatic haemangioma
iii. Wilson's disease vi. Neonatal haemachromatosis
163
ANSWER TO CASE 4.19
v. Hepatic haemangioma.
D Fifty per cent of children with hepatic vascular tumours also have cutaneous haeman
C
(1)
giomas. Liver haemangioendotheliomas present with the above features, the median
� age at presentation being 1 month and 70% of infants having high output cardiac failure
o· on presentation. The diagnosis would be supported by the presence on clinical exami
::::i
VI
0,
nation of a bruit over the liver. The investigations required usually include liver ultra
::::i sound, Doppler imaging, contrast CT and arteriography.
a.
)> Complications include congestive heart failure, consumptive coagulopathy and micro
::::i
VI angiopathic anaernia. There may also be increasing mass effects: abdominal distension,
�
(1) obstructive jaundice, vomiting due to GI tract obstruction.
-,;
VI
--h Treatment depends on symptoms. Medical treat1nent for symptomatic, but non-life
0
-,; threatening lesions with steroids or a-interferon and for life-threatening lesions, embol
,-+
:::::; isation, hepatic artery ligation or surgical resection.
(1)
z
(1)
�
,,
0
3
0,
,-+
m
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0,
3
164
minutes 0: 138
20 minute uptake � 31%

60mn/30mn ratio � 45%
cstd0002i
Fig 4.20
A 2-week-old baby boy was referred urgently to the endocrine clinic as he had been
found to have a TSH of 70 IU/ml on the neonatal screening test. He was born by
normal vaginal delivery at term and is bottle-fed. He is not jaundiced or constipated.
There is a family history of deafness with two of his mother's cousins wearing hearing
aids from early childhood. The older sibling of the patient has diabetes. The mother's
grandmother was thought to have a swelling in her neck.
On examination, the baby was found to have a large swelling in his neck. The rest of
his systemic examination was normal.
The figure shown is of a perchlorate discharge scan showing rapid uptake of
radioactive iodine with 45% discharge of iodine 1 h after perchlorate was given.
What is the diagnosis?
i. Congenital hypothyroidism secondary to thyroid agenesis
ii. Congenital hypothyroidism secondary to iodine deficiency
iii. Congenital hypothyroidism secondary to dyshormonogenesis
iv. Normal perchlorate scan
165
ANSWER TO CASE 4.20
iii. Congenital hypothyroidism secondary to dyshormonogenesis
,0 In the UK, goitre is a rare finding in the neonatal period, which suggests an inborn
C:
error in thyroid hormone synthesis (iodine deficiency occurs in some areas and can
�
11)
o·
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also present with goitre). These defects are commoner in consanguineous marriages.
The perchlorate discharge scan is a useful tool for detection of dyshormonogenesis.
V)
OJ
The perchlorate ion competes with iodide for trapping by the thyroid follicular cell
::J plasma membrane and the discharge of iodine occurs, which can be monitored by
a..
release of radiation from the gland. Further investigations include FT4 and repeat TSH,
)>
::i
V)
ultrasound scan of the thyroid gland, a radio-iodine scan and a hearing test.
11) Congenital hypothyroidism is inadequate thyroid hormone production in newborn
'""I
V)
infants. This can occur because of an anatomic defect in the gland, an inborn error of
-+,
0
'""I
thyroid n1etabolism, or iodine deficiency. The incidence is 1 : 3-4000. The thyroid
,-+ gland uses tyrosine and iodine to make thyroxine (T4) and triiodothyronine (T3).
:::::r
11) Iodide is actively taken into the thyroid follicular cells and then oxidized to iodine by
z
11)
thyroid peroxidase. Organification occurs when iodine is attached to tyrosine n10lecules
attached to thyroglobulin, finally forming tetraiodothyronine (i.e. T4). TSH activates
.,,
0
enzymes needed to cleave T3 and T4 from thyroglobulin .
3 Inborn errors of thyroid metabolism can result in congenital hypothyroidism in children
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,-+ with anatomically normal thyroid glands. Iodine deficiency during fetal and postnatal
m
>< life causes goitre and hypothyroidism_.
OJ
3 Aetiologies: excluding iodine deficiency, congenital hypothyroidism_ can caused by:
Dysgenesis of the thyroid gland
o Agenesis of or ectopic thyroid
Inborn errors of thyroid hormone metabolism (dyshormonogenesis)
o TSH receptor abnonnalities, abnormal iodide uptake, peroxidase or organifica
tion defects (i.e. inability to convert iodine to iodide) such as Pendred sydrome -
associated with congenital deafness
Thyroid hormone resistance (thyroid hormone receptor abnormalities)
Maternal autoimn11me disease (transient or permanent)
TSH or TRH deficiencies, e.g. hypopituitarism
Iatrogenic causes (maternal use of thioamides, iodine excess, radioactive iodine
therapy)
166
CASE 5.1
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Fig 5.1.A Fig 5.1.B
A distraught single mother brought her 8 month old to the A&E department very
worried about lesions that looked like burns and just appeared out of nowhere (Fig.
5.1.A). The child was fully immunised, born to non-consanguineous parents and bottle
fed. The child was not left unsupervised at all according to the mother, and she clearly
recalls the absence of these lesions 24 h before.
While an inpatient, newer lesions appeared (Fig. 5.1.8).
Which of the following should be considered in the differential diagnosis?
i. Scarlet fever
ii. Pomphylox
iii. Impetigo
iv. lncontinentia pigmenti
v. Dystrophic epidermolysis bullosa
vi. Staphylococcal scalded skin syndrome
vii. Bullous pemphigoid
169
ANSWERS CASE 5.1
iii. Impetigo
vi. Staphylococcal scalded skin syndrome
,0
C: Differential diagnosis of generalised exfoliation includes drug-induced and virus
<D
� mediated toxic epidermal necrolysis, burns, epidermolysis bullosa, bullous erythema
o· multiforme and diffuse cutaneous mastocytosis as well as staphylococcal scalded skin
:::,
Vl
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syndrome (SSSS) and impetigo.
::,
Q.. Treatment of SSSS involves i.v. flucloxacillin and supportive therapy. SSSS is a disease
)> primarily affecting infants and young children. In the infant, the lesions are mostly
:::,
found on the perineum or periurnbilically, or both, while the extremities are more
commonly affected in older children. The disease begins with erythema and fever,
.....
Vl followed by formation of large fluid-filled bullae, which quickly rupture on slightest
-+,
0
..... pressure (Nikolsky sign) to leave extensive areas of denuded skin. The form and severity
r-+ of SSSS will vary with the route of delivery of the toxin to the skin, ranging fr01n the
:::,
(I) localised bullous impetigo to generalised SSSS involving the entire skin surface. In the
z latter, patients are prone to poor temperature control, extensive fluid losses and second
(I)
� ary infections. They may also develop sepsis and present with hypotension, neutropenia
-n and respiratory distress. Antibiotic treatment with �-lactamase-resistant semisynthetic
0
3
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penicillins such as flucloxacillin is usually effective.
r-+
m
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3
170
CASE 5.2
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N
Fig 5.1
A 3-week-old baby presented with a large bruise-like swelling overlying the right thigh
that had developed quickly over 3 days. The baby had been delivered by Caesarean
section for failure to progress. At birth, a small mark had been noted at the same site.
It was thought to be due to trauma during the Caesarean section. The baby was given
intramuscular vitamin K in the contralateral thigh. On examination, the leg was held in
flexion and there was a large hard mass that appeared to involve the upper thigh,
lower abdominal wall and scrotum.
The child appeared otherwise well with no circulatory compromise.
The results of investigations were:
Hb 7.6 g/dl
wee 12.4 x 109;1
The blood film was reported as showing red cell fragmentation and no evidence of
platelet clumping.
Clotting profile:
APTT >180 s
PT >30 s
Fibrinogen >0.1 g/1
i. Spreading cellulitis
ii. Maternal thrombocytopaenia with transplacental transfer of antibodies
iii. Von Willebrand's syndrome
iv. Kasabach-Merritt syndrome
v. Haemophilia B
171
ANSWERS CASE 5.2
iv. Kasabach-Merritt syndrome
0 This child has apparently developed a large swelling, which may be a haematoma so
C
(D
clotting investigations are 1nandatory. FBC will help to shmv whether a significant
� amount of blood has been lost. Ultrasound of the lesion will help to quantify its size
a· and extent - in this child, it extended up to the lower poles of both kidneys in the
::::::i
V'I
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retroperitoneum.
::::::i
D.. Later MRI enhanced v.rith contrast will be helpful in the management of this
)> condition.
::::::i
� The diagnosis here is Kasabach-Merritt syndrome. This child has a rapidly proliferating
�
V'I
haemangioma (histology vvhen performed showed this to be kaposiform haemangioen
-+, dothelion1a) and a consumptive coagulopathy.
0
'""'I
r-+ Management options include high-dose oral steroids. Only correct clotting abnorn1ali
::;
(D ties and platelet count if the child is actively bleeding. If the lesion does not respond
z
(D
to oral steroids then i.v. methylprednisolone may be required. Other possible therapies
:;E include vincristine, ex-interferon, radiotherapy, amputation and embolisation.
,,
0 The prognosis of these lesions is very variable. Some authors quote 20-30% n1ortality.
3 Older papers quote 60%. It is probably dependent on the initial size of the lesion with
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r-+ retroperitoneal lesions faring worse.
m
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172
CASE 5.3
�
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()
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()
I
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a,
r-+
N
Fig 5.3
A newborn baby presented at birth with the skin lesion shown.

a. What is the principal lesion?
i. Port-wine stain (naevus flammeus)
ii. Telangectatic naevus
iii. Giant melanoc ytic naevus
iv. Mongolian blue spot
v. Strawberry naevus
b. Which two investigations would you request?
i. Karyotype
ii. Head MRI
iii. Spinal MRI
iv. FBC
v. Head ultrasound
vi. Lumbar X-ray
173
ANSWERS TO CASE 5.3
a. i. Port-wine stain (naevus flammeus)
b. iii. Spinal MRI
0 iv. FBC
C:
�
(I)
This photograph shows a port-wine stain of the lumbosacral area. Port-wine stains are
o·
:::::i
present at birth. They are large, irregular, deep red macular lesions and represent a
VI
OJ
vascular malformation involving mature dilated dermal capillaries. The lesions are
sharply circumscribed and vary tremendously in size. Most of the lesions are present
c..
:::::i
on the head and neck, most are unilateral, and in general the lesions deepen in colour
)>
:::::i with age. The most effective treatment is pulsed dye laser therapy, which avoids thermal
� injury to the surrounding tissue and leads to improvement without scarring. Major
.....
(I)
VI
morbidities (in the absence of syndromic or other associations) include poor self-image
-I-, and traumatic bleeding.
0
.....
r+ Investigations required include an MRI of the lun1bosacral spine (maybe ultrasound of
:::,
(I) the lun1bosacral area) and a FBC to exclude Kasabach-Merritt syndrome (haen1angioma
z associated with thrombocytopenia).
�
(I)
Haemangiomas over the lumbosacral area are associated with spinal dysraphism., which
"TI
0 is a general term for coexistent vertebral and spinal cord defects. Spina bifida occulta
3 is the rnost con1.mon and benign defect, but other lesions include intradural and extra
OJ
r+ dural lipomas, cysts, teratomas and tethering of the spinal cord. MRI of the spine is
m the investigation of choice.
><
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3
174
s:
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n
I
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,-+
N
Fig 5.4
It is the middle of a particularly hot summer when a 5-year-old girl presents with a 2-
month history of being profoundly miserable and tired. Her parents have noticed a rash
on her face but felt this was due to sun exposure. Previously a very active child, she is
now lethargic, and her mother has noticed particular problems on getting out of bed
and going upstairs. Her GP has taken some routine blood samples and was surprised to
find that her CRP level was 156. The rash found on her hands is shown. Neurologically,
she has profound proximal muscle weakness.
i. Juvenile dermatomyositis
ii. Myotonic dystrophy
iii. Post-viral syndrome
iv. Guillain-Barre syndrome
v. Systemic lupus erythematosus
vi. Polymyalgia rheumatica
175
I
ANSWER TO CASE 5.4
i. Juvenile dermatomyositis.
Juvenile dermaton1yositis is a multisystem disorder that results in inflammation of the
C
<D skin, striated nrnscle and gastrointestinal tract. The exact aetiology is unkno,vn, but
� research is focused on abnormalities of cell-mediated imnrnnity and imrnune complex
o· disease; infection rnay also have a role. The onset is common between the ages of 4
::::i
VI
OJ
and 10 years, and the condition is more frequent in girls.
:::;
0... Juvenile dermat01nyositis usually presents with a combination of malaise, fatigue, fever,
)> profound flexor nrnscle weakness and rash. The rash is often pathogno1nic, with a
:::;
VI heliotrope discolouration around the eyes, Gottren's papules (shiny, erythematous
� plaques on the extensor surfaces of the finger joints and other extensor sur£'lces) and
�
VI nailfold capillary loop dilatation. The flexor muscle weakness is shown by a positive
-+-,
0
"""i
Gower's sign, an inability to flex the neck off pillows, difficulty going upstairs, etc.
,-+ One of the con1plications of this disease is calcinosis (subcutaneous or within the muscle
:::;
<D layers). Dermato1nyositis can also be complicated by dysphagia, puln1onary restriction,
z
<D
muscle atrophy and contractures and lipoatrophy.
�
.,,
0
Laboratory tests often (although not always) show a high level of muscle enzymes
(creatinine kinase) as well as elevated inflammatory niarkers. An electromyogran1 can
3OJ also be helpful. Magnetic resonance mapping shows myositis. If the diagnosis is uncer
,-+ tain, an ultrasound-guided muscle biopsy can be pe1formed.
m
><
OJ Treatment must be multidisciplinary. Medical treatn1ent aims to reduce inflammation
3 using prednisolone, hydro::-...1chloroquine, methotrexate (and other second-line agents)
and immunoglobulin. The outcome varies according to the course of the disease. Many
have limited disease and the outcome is excellent; a small percentage, however, develop
aggressive disease and require ongoing support. Mortality is approxin1ately 5% and
usually follows pulmonary insufficiency, acute gastrointestinal bleeding or sepsis.
176
CASE 5.5
s:
;:i:,
11
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11
I
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ni
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N
Fig 5.5
A 5-year-old girl was brought to the paediatrician by her professional parents. Her
symptoms included intermittent dribbling, dysuria and urgency. Her GP had treated her
with several courses of antibiotics for symptoms suggestive of urinary tract infections.
Only one of numerous mid-stream urine specimens had isolated organisms. Her school
work was deteriorating. Her growth and blood pressure were normal. Inspection of the
urogenital region revealed no dribbling and looked as shown.
What abnormal features can you see?
i. Gaping and scarred hymen
ii. Threadworms
iii. Lichen sclerosis
iv. Posterior healed transection of hymen
v. Foreign body
177
ANSWERS TO CASE 5.5
i. Gaping and scarred hymen
iv. Posterior healed transection of hymen
0
C The photograph shows a markedly attenuated scarred hymen with a posterior healed
tD
� transection at the 7 o'clock position. There is also a gaping hymenal orifice.
o·
::::I
V'l These findings are consistent with penetrative traun1a and probable sexual abuse.
OJ
::::I Further steps to be taken include:
Cl.
a full paediatric assess1nent for evidence of associated physical abuse
)>
::::I
V'l
explanation of concerns to parents and why child protection services nmst be
� contacted
�
V'l
referral to a paediatrician experienced in dealing with sexual abuse
-h screening for sexually transmitted disease
0
"""I evaluation of siblings should be considered
,-+
::::r involvement of the child and family mental health team
tD
z Child sexual abuse in young children can present with symptoms suggestive of urinary
tD
tract infection, urinary incontinence, deterioration in school work and behavioural
-r, changes. Allegations by young children of intrafamilial sexual abuse are uncommon.
0
3 The attenuated hymen which indicates loss of tissue and the posterior healed transec
OJ
,-+ tion are clinical evidence of penetrative trauma. A gaping hyn1enal orifice should not
m be used as a sole basis for diagnosis as assessment is not always reliable. The findings
><
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in this child are not possible to date.
3
Although the parents have to be informed about suspicion, utmost care should be taken
to ensure that the child is not put at further risk. The child's welfare is paramount and
screening for sexually transmitted disease should be carried out. A police surgeon n1ay
be asked to assist a paediatrician who doesn't have relevant forensic expertise. As there
is no allegation and no clinical evidence of recent assault, forensic samples rnay not be
indicated.
Other siblings may need to be evaluated as it is likely that they may also be being
abused. A referral to the mental health team should help with assessing any psychologi
cal and emotional needs of the child and family.
178
CASE 5.6
s:
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n
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n
I
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,-+
N
Fig 5.6
A baby was delivered by emergency Caesarean section at 34 weeks' gestation

following decreased fetal movements for 2 days and a poorly reactive cardiotocogram.
She required full resuscitation and was found to have a Hb of 2.3 g/dl. She was not
hydropic and did not have hepatosplenomegaly.
What does this blood film (Kleihauer test) show?
i. Acute haemolysis
ii. Positive Coombs' test
iii. Microcytic hypochromic anaemia
iv. Sickling
v. Feta-maternal haemorrhage
vi. Haemolytic disease of the newborn
ANSWER TO CASE 5.6
v. Feta-maternal haemorrhage
.0 Profound fetal anaemia can be due to haemorrhage or haemolysis or failure of produc
C:
(I)
tion, e.g. parvovirus infection. Haen10rrhagic causes include fetomaternal transfusions,
� twin-to-t,vin transfusions, fetoplacental transfusion at birth, fetal haemorrhage due to
o·
::::l
placenta praevia, placental abruption or placental injury during Caesarean section.
V\
OJ
Perinatal hae1norrhages can be intracranial, subaponeurotic, intra-abdominal or due to
umbilical cord rupture. Absence of hepatosplenomegaly and hydrops makes haemolysis
c..
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and failure of production unlikely in this case.

)>
::::l
Investigations include FBC and film, blood group (maternal and fetal), direct Coon1bs'
test, serum bilirubin, maternal Kleihauer, coagulation screen and ultrasound scans to
.,
(I)
V\ search for concealed haernorrhage.
-h
0
., The figure shows the Kleihauer test, prepared from the maternal blood film, which
r+
::::; has been stained with eosin and treated with acid. The acid elutes adult haemoglobin
(I)
leaving "ghost cells". Fetal cells retain the stain since fetal haemoglobin is acid resistant.
z
(I) The volun1e of transfusion can be estin1ated from a differential count of n1aternal and
,,
0
fetal cells. This together with a negative direct Coombs' test and normal bilirubin
suggest a feto-n1aternal haemorrhage. In this case, it was an estimated 380 ml. This is
3 greater than the circulating volume of the baby as the fetal red cells may survive 1nany
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r+ weeks.
m
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3
180
CASE 5.7
�
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,-+
N
Fig 5.7
A 5-year-old girl returned from a holiday in Jamaica with her parents 4 weeks ago. Her
mother reported that an ant had bitten her on the beach. Two weeks later she
developed a lesion on her foot. It was itchy and spreading.
i. Schistosomiasis
ii. Scabies
iii. Erythema marginatum
iv. Cutaneous larva migrans
v. Lyme disease
b. What is the underlying cause?
i. Sarcoptes scabiei
ii. Streptococcal infection
iii. Trichuris tricuria
iv. Borrelia burgdorferi
v. Ancylostoma braziliense
181
ANSWERS TO CASE 5.7
a. iv. Cutaneous larva migrans
b. v. Ancylostoma braziliense
.c)
C
(1) This is an example of cutaneous larva migrans. This is caused by skin infestation with
� hookworm or roundworm larva. Cutaneous larva migrans may well be seen in children
o· in the UK because of increased travel to exotic destinations. The usual agent is Ancy
::,
V)
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lostoma braziliense, a hookworm found in cats and dogs. It is endemic in southern areas
::, of the United States, in Central and South America, and in other subtropical areas.
0.
Ancylostoma caninum is much less common in these areas but is ubiquitous in dogs and
)>
::, cats in Australia. In warn1, moist sandy soil the eggs mature into filariform larvae, which
�
t1)
penetrate the skin. After a few days the larvae begin migration in the base of the epi
-,
V) dermis, moving as much as several centimetres daily. The larva is 1-2 cm beyond the
-+, advancing edge of the lesion. Treatment is with thiabendazole. Topical thiabendazole
0
-, cream is probably the treatment of choice. Oral thiabendazole is associated with gas
,-+
:::; trointestinal side effects.
t1)
z
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182.
'._ CASE 5.8
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Fig 5.8
A well, term baby girl was reviewed following delivery because of a generalised rash
(see photo). Her mother had a history of recurrent miscarriages but this pregnancy had
been uncomplicated.
i. lncontinentia pigmenti
ii. Disseminated herpes simplex infection
iii. Neonatal urticaria
iv. Infantile pomphylox
v. Eczema herpeticum
183
ANSWER TO CASE 5.8
i. lncontinentia pigmenti
.0 Differential diagnosis of this generalized bullous eruption includes infectious causes,

C:
(I)
e.g. staphylococcal bullous i1npetigo, herpes sin1plex (neonates likely to be umvell), and
� non-infectious diseases, e.g. incontinentia pigmenti (the diagnosis in this case) and
o· epidermolysis bullosa.
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lncontinentia pign1enti, also known as Bloch-Sulzberger syndrome, is a rare disorder
Q_ characterised by abnormalities in ectodermal tissues including skin, eyes, CNS and
)> dentition. It is inherited as an X-linked dominant disorder which is usually lethal in
::,
male fetuses. In the neonatal period, the skin lesions are characteristically bullous and
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(I) it is an important differential diagnosis in any baby with a vesicular rash.
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184
CASE 5.9
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Fig 5.9
A 6-year-old girl was brought to A&E by her mother one evening, who had noted
drops of blood on her knickers and "itching below". There was some dysuria, but no
discharge. As usual, her uncle had taken her to school that morning. He had reported
to her mother that the child had tripped and fallen on a concrete step. The duty
paediatric registrar is asked to see her. The figure shows the appearance of her external
genitalia.
a. What does the picture show?
i. Vulvitis
ii. Candida infection
iii. Cliteromegaly
iv. (Vulva!) lichen sclerosus et atrophicus
v. Ragged, torn hymen
b. Which important diagnosis must also be considered?
i. Urinary tract infection
ii. Threadworms
iii. Sexual abuse
iv. Trauma
v. Ovarian failure
185
ANSWERS TO CASE 5.• 9
a. iv. Lichen sclerosus et atrophicus
b. iii. Sexual abuse
This picture shows haemorrhagic vulval lichen sclerosus et atrophicus. This condition
is seen in pre-pubertal girls and post-menopausal women. Initially white papules appear
which then join to form plaques. Haemorrhagic areas may also be present. These are
cu part of the disorder and not secondary to scratching. Marked itching and vulval sore
:::> ness are presenting symptoms, and scratching and rubbing may lead to bleeding of the
a.
fragile skin. There 1nay well be a family history of lichen sclerosus. Treatment is with
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:::, topical steroids. Resolution occurs at or just after the menarche.
� The possibility of sexual abuse must also be considered, and in fact, the two conditions
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may co-exist, as the trauma related to sexual abuse may act as a trigger to developing
-
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"""' lichen sclerosus, related to Koebnerization, which is known to occur in this disease. It
,-+ is important to elicit a full history regarding the extent of the trauma - was it a straddle
:,-
Cl) injury? Did she appear to have painful external genitalia following the incident?
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Minimal trauma can cause bleeding and acute inflanuT1ation in the presence of lichen
sclerosus but a straddle injury could explain inflammation or injury to the hyn1en.
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0 Are there any long-standing concerns about this child from mother or school? For
3
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exan1ple, any deterioration in schoolwork or behavioural problems. Ask about the
,-+ dysuria and symptoms of a urina1y tract infection, and find out more about the itching
m - over labia or anus? Night or day, or both? Intennittent or longstanding? Thread
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cu worms need to be excluded as a co-existing cause for the itchiness.
3
General examination, and examination of the external genitalia and anus using a mag
nifying light source is important; this should be done with the consultant present in
child sexual abuse, to avoid repeated exa1ninations. Investigations should include mid
stream urine to exclude a urina1y tract infection, and a tape slide to exclude thread
worms. If there is a histo1y of vaginal discharge, a swab should be taken.
The child should be discharged ,to a place of safety, with careful follow-up. Do bear
in mind that it is possible to have a hymen of normal appearance with sexual abuse,
and lichen sclerosus and sexual abuse are not mutually exclusive diagnoses.
186
CASE 5.10
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Fig 5.10.2 \
6
Fig 5.10.1
Fig 5.10.3
Choose the name and recognised association of each of these three dermatalogical
lesions:
a. Strawberry naevus i. May be associated with calcification of the
b. Melanocytic naevus leptomeninges
c. Port-wine stain ii. May be associated with Kasabach-Merritt syndrome
iii. Is potentially premalignant
Figure 5.10.1: a. and ii. "Strawberry naevus" and "May be associated with the
0 Kasabach-Merritt syndrorne"
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Figure 5.10.2: c. and i. "Port-wine stain" and "May be associated with calcification
o·
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of the lepton1eninges"
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Figure 5.10.3: h. and iii. "Melanocytic naevus" and "Is potentially premalignant"
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0.. Figure 5.10.1 is a strawberry naevus, the n1.ost conm1.on of the capillary haemangiomas.
)> It usually presents as a small red papule which develops at or soon after birth, and
:,
increases in size for a few years. It then gradually involutes to leave an excellent cos
� metic result. The incidence is 1 : 20 babies. A minority will cause problems such as
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bleeding, ulceration and disfigurement. Other complications are visual impairment or
airway obstruction depending on the site of the haemangioma. Rarely the lesion may
,-+ be extensive and the abnormal vessels may sequester platelets causing thrombocytopae
::::;
(I) nia and a petechial rash (Kasabach-Merritt syndrome). For lesions likely to cause
z problems, early treatment with oral or intralesional steroids, a-interferon and laser
(I)
therapy should be considered.
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0 Figure 5.10.2 is a port-wine stain, a vascular malformation. This has an incidence of
3
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3: 1000 births. It is a macular red or purple area which often affects one side of the
,-+ face. It is usually present at birth and stays the same size relative to the head size as
m the child grows. The condition persists throughout life, becoming darker and thicker
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QJ with age, and can be very disfiguring. Pulse dye laser therapy is the treatment of choice
3 and younger children respond better. A facial port-wine stain can be associated with
angiomatosis and calcification of the leptomeninges over the cerebral cortex. The
patient may present with convulsions, hemiplegia and mental retardation (Sturge
Weber syndrome). All children with a facial port-wine stain on the upper part of the
face and scalp should have a baseline MRI scan looking for central nervous system
involvement.
Figure 5.10.3 is a melanocytic naevus. This naevus is due to a developmental defect
causing benign localised proliferation of the melanocytes in the dermis. Melanocytic
naevi vary considerably in size and appearance. They are potentially premalignant.
Extensive, deeply pigmented, hairy naevi which are present at birth seem more likely
to become malignant.
188
CASE 5.11
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Fig 5.11
A 5-year-old child of Indian parents has recently returned from visiting family in rural
India. He has had a fever for 48 h, but has no focal symptoms. On examination he has
a temperature of 41°C, with 3 cm splenomegaly, and no rash. He does not appear
particularly unwell. Investigations show:
Hb 9.3 g/dl
WBC 10.5 x 109/1
CRP 8 mg/I
A blood film demonstrating the condition is shown.
i. Typhoid fever
ii. Paratyphoid
iii. P. falciparum malaria
iv. P. vivax malaria
v. Dengue fever
vi. Yellow fever
189
TO CASE 5.11
iii. P. falciparum malaria
I:) Im.portant information to elicit to aid in making the diagnosis would be any history
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of antim.alarial prophylaxis, which antimalarials had been used, and if so whether they
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were taken at least a week prior to travelling and 4 weeks following return. Also, any
o·
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contact with known febrile illness may also be relevant.
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a.
::::::i
malaria parasites which need to be done rapidly, as complications may occur within
)> hours of symptoms first occurring. As a negative film does not exclude malaria, at least
::::::i
three films should be taken in potential cases. Alternative differential diagnoses (e.g.
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(I) typhoid fever) may prompt other investigations, particularly culture of blood and urine.
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Rapid blood antigen detection methods for malaria are now available, and are becom
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ing a useful adjunct to aid diagnosis. The diagnosis here is P. falciparum malaria, as
r+ there are multiple ring forms in red cells on the thin film.
:::;
(I)
Managing the child with malaria needs to be undertaken in hospital. Although chlo
z roquine was historically the drug of choice for uncomplicated m.alaria, it is no longer
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(I)
recommended as resistance is comm.on worldwide. Quinine for 5 days or until the

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0 blood film is negative, followed by a single dose of sulphadoxine pyremethamine
3 (Fansidar) is the appropriate treatment for imported malaria managed in the UK, and
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r+ in an uncomplicated case could be given orally in hospital. An alternative treatment
m for children over 2 years would be mefloquine. Up to date, telephone advice on the
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management of malaria, (and its prophylaxis) is available from the Schools of Tropical
3 Medicine in Liverpool and London.
There are about 300 cases of malaria in children each year in the UK, half of whom
did not take antimalarial prophylaxis. However, chemo-prophylaxis does not guarantee
protection against malaria. With increasing antimalarial resistance, breakthrough infec
tion is well recognised. Antimalarials should be continued for 4 weeks after returning
from a malarious area. For this child with P. falciparum malaria no further treatment
is required, but a film should be examined at the end of treatment, and after 4 weeks
(or with subsequent fever) to ensure eradication. Had the child developed P. vivax
infection, this is mostly chloroquine sensitive, but resistant strains are described from
India. P. vivax also requires a 2-3 week course of primaquine orally to clear the hyp
nozoite stage from the liver. Dormant hypnozoites of P. vivax cause relapse, but are
not present in the life cycle of P. falciparum. This child could have a mixed infection
with P. vivax, which may declare itself some months later after treatment has
stopped.
CASE 5.12
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Fig 5.12
This 6-month-old male infant was referred to a paediatric outpatient clinic for eczema
in the perioral, post auricular and perinea! regions. He also had intermittent diarrhoea.
The use of various moisturisers and topical hydrocortisone cream did not improve it. He
had fallen below the 2 nd centile for weight and was on the 10th centile for length. On
examination, he had scanty scalp hair.
a. What is the rash due to?
i. Seborrhoeic eczema
ii. Iron deficiency
iii. Zinc deficiency
iv. Latex allergy from teat of bottle
v. Infected eczema
vi. Staphylococcal infection
b. What are the other manifestations of this condition?
i. Constipation
ii. Nail pitting
iii. Corneal opacities
iv.. Irritability
v. Anorexia and failure to thrive
vi. Deranged coagulation
c. How may the condition be inherited?
i. Autosomal recessive
ii. No genetic link
iii. Autosomal dominant
iv. X-linked acquired form
a. iii. Zinc deficiency
b. iv. Irritability
,0 v. Anorexia and failure to thrive
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c. i. Autosomal recessive inheritance
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a· Zinc deficiency can be either congenital or acquired. The acquired form of zinc defi
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ciency is more common. The rash due to zinc deficiency has a peculiar perioral dis
::, tribution that is smooth and shiny unlike the rash of eczen1a, which usually occurs in
a.
the flexures in this age group. This infant's zinc level was 2 µmol (normal range
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8-16 µn10l).
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n1ediated inununity and chemotaxis with recurrent infection, anorexia and failure to
r-+ thrive, hypogonadisn1 and corneal changes and nyctalopia (im_paired vision in the
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(I) dark).
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(I) Zinc deficiency can be acquired secondary to nutritional deficiency, but can also be
� inherited as a congenital forn, called acrodermatitis enteropathica. It results from an as
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recessive 1nanner.
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192
CASE 5.13
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Fig 5.13
An 8-year-old girl was admitted with a 2-day history of intermittent crampy abdominal
pain and passing fresh bloody stools. Other than seasonal colds she had been well,
with no recent weight loss, no other bleeding sites and no previous episodes. Initial
investigations revealed normal FBC and film, normal serum U&E, albumin 32 g/I and
other LFTs were normal.
a. Which of the following would be included in your initial differential
diagnosis?
i. Acute appendicitis
ii. Giardiasis infection
iii. Salmonella infection
iv. Meckel's diverticulum
v. lntussusception
vi. Inflammatory bowel disease
vii. Diverticular disease
b. What other investigations would you do initially?
i. Coagulation screen
ii. Abdominal X-ray
iii. Upper GI endoscopy
iv. Inflammatory markers
v. Colonoscopy
vi. Abdominal ultrasound scan
vii. Stool for faecal occult blood
Her symptoms settled spontaneously and she was discharged after 48 h to be seen
again as an out-patient. However, 2 days later she presented with a rash as shown in
Figure 5.13.a and b.
c. What is the most likely diagnosis?
i. Inflammatory bowel disease
ii. Polyarteritis
iii. Henoch-Schbnlein Purpura
iv. Von Willebrand's disease 193
v. Haemophilia A
a. iii. Salmonella infection
0 v. lntussusception
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o· iv. Inflammatory markers

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Causes which need to be considered in this case include infective (salmonella, E. coli,
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etc.), surgical (fissure, polyp, intussusception, Meckel's diverticulum) and inflammatory
bowel disease.
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Stool should be sent for microscopy and culture plus virology. If bleeding is significant
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a sample should be sent for cross-match.
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(1)
also be checked.
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:§: An ultrasound scan is generally of more help than an X-ray (which also confers a dose
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of radiation).
3 The rash, which is a non-tender purpuric rash (mainly on extensor aspects of legs and
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,-+ buttocks) is Henoch-Schonlein Purpura. It is important to n1easure blood pressure and
m dip the urine for blood and protein, both of which signal renal involvement, which
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will need follow-up.
3
GI involvement is comn10n in Henoch-Schonlein Purpura, and bleeding from the gut
may be occult or frank, secondary to the vasculitic process or to intussusception of the
colon. The colicky abdominal pain may be treated with simple analgesia and some
elect to treat with steroids if the symptoms are severe. The associated complication of
intussusception can be difficult to rule out and if in doubt paediatric radiological and
surgical opinions should be sought.
The prognosis for gut involvement is good, with resolution of the symptoms over
weeks to months as the vasculitic process settles.
194
CASE 5.14 .·
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Fig 5.14
A term baby boy delivered by SVD was noted on routine post-natal examination to
have an unusual rash. His mother was a 22-year-old primigravida with no significant
past medical or family history. This pregnancy had been uncomplicated.
a. What further investigations should be requested on the mother?
i. Anti-Ro antibodies
· ii. Rheumatoid factor
iii. Antinuclear antibodies
iv. Anti-La antibodies
v. Viral titres
vi. ECG
b. What further investigations should be requested on the baby?
i. FBC
ii. Blood cultures
iii. EEG
iv. CXR
V. ECG
vi. Cranial ultrasound scan
,....
I
195
a. i. Anti-Ro antibodies
iv. Anti-La antibodies
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� v. ECG
a· The abnormalities shm;vn are a butterfly facial rash and discoid erythematous patches.
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0) Differential diagnosis includes neonatal SLE or staphylococcal skin sepsis. To investigate
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c.. for maternal SLE, anti-Ro and anti-La antibodies must be checked.
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� of thrombocytopenia, and LFTs for evidence of hepatitis.
'""
(1)
VI Neonatal SLE can present in infants of asymptomatic rnothers (as in this case) as well
-
0 as in those with established disease. It occurs as a result of transplacental transfer of
'""
,-+ rnaternal autoantibodies, particularly Ro and La autoantibodies. It is characterised by
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iary disease and thrombocytopenia.
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196
CASE 5.15
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Fig 5.15
This 8-year-old boy presented with a widespread rash following a mild upper
respiratory tract infection, associated with conjunctivitis and oral lesions.
i. Toxic epidermal necrolysis
ii. Stevens-Johnson syndrome
iii. Gingivostomatitis
iv. Herpes zoster
v. Reiter disease
b. Choose two known causes of this rash:
i. Vancomycin
ii. Latex allergy
iii. Gluten enteropathy
iv. Leukaemia
v. Streptococcal infection
vi. Varicella infection
197
a. ii. Stevens-Johnson syndrome
b. iv. Leukaemia
D v. Streptococcal infection
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This child has Stevens-Johnson syndrome (erythema multiforme major). It is generally
regarded as a hypersensitivity reaction to various medications, infections and toxic
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substances, such as nitrobenzene, and radiation therapy. Drugs irn_plicated in its aetiol
:::, ogy include penicillin, sulphonamides, isoniazid, tetracyclines, phenytoin, carbamazepine,
0.
captopril, aspirin and etoposide. Infections include herpes simplex 1 and 2, mycoplasma
)>
:::, pneumonia, group B strep, BCG vaccine, yersinia and enteroviruses. It is also seen in
patients with leukaemia and lymphoma. Stevens-Johnson syndrome is a serious disorder
(I)
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in which at least two mucous membranes, as well as skin, are involved. Clinically it
-+, presents as a widespread erythematous rash with target lesions (central vesicular or
0
'""I erythe1natous area surrounded by concentric rings of pallor and erythema), purulent
,-+
:Y conjunctivitis and lesions on the oral mucosa. The classic lesions usually appear follow
(I)
ing a prodromal respiratory illness. New lesions occur over 1-4 weeks with healing
z
(I) over 6 weeks. Treatn1ent might include i.v. fluids, systemic and topical antibiotics and
skin care.
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Differential diagnosis of this rash would include toxic epidennal necrolysis, gingivos
tomatitis, Reiter disease and benign mucous membrane pe1nphigoid.
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198
CASE 5.16
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Fig 5.16
This 2-year-old presented to the A&E department with bilateral conjunctiva!

haemorrhages, and periorbital bruises. She attended with her mother and stepfather
who said they first noticed her appearance when she woke up in the morning. There
was no history of trauma. The parents reported that she was happy and well in herself,
except for a nagging harsh cough for the previous 2 weeks. Apart from the appearance
of her eyes, her examination was entirely normal. A blood count showed:
Hb 10.0 g/dl
wee 2s x 109/1
Neutrophils 3.1 x 109/I
Lymphocytes 21.2 x 109/I
What other investigation would you perform?
i. Blood culture
ii. Pernasal swab
iii. Urine for catecholamines
iv. Skull X-ray
v. Nasopharyngeal aspirate
199
ANSWER TO CASE 5.16
ii. Pernasal swab
D This little girl had pertussis infection (whooping cough). A pernasal swab should be
C:
sent for Bordetella pertussis.
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(I,)
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The possibility of non-accidental injury nrnst be excluded. However, examination was
:,
VI othenvise entirely normal and there ,vere no other concerns. Should there be any
OJ concerns, a skeletal survey and ophthalmological examination should be arranged, and
:,
0.. referral made to social services. On observation, her cough was parm,.ysmal in nature,
)> with occasional, but definite episodes of whooping. The lymphocytosis further sup
:,
ported the diagnosis, and after 7 days, her pernasal swab confirmed growth of Bordetella
-
� pertussis. Conjunctival haemorrhages are a recognised complication of whooping cough,
""'
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200
CASE 5.17
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Fig 5.17
A 10-year-old girl presents with this vasculitic facial rash which has been worsening
over several months. On examination in addition to the facial rash, she is found to have
stigmata of chronic liver disease with spider naevi, leuconychia and mild clubbing. She
also has a 7 cm spleen palpable, though only a firm liver edge. Her LFTs are as follows:
Bilirubin 35 µmol/I
ALT 185 U/I
AST 212 U/I
GGT 24 U/I
ALP 400 U/I
Albumin 36 g/I
i. Gilbert's syndrome
ii. Wilson's disease
iii. Autoimmune hepatitis
iv. SLE
v. Haemochromatosis
vi. Biliary cirrhosis
201
ii. Wilson's disease
iii. Autoimmune hepatitis
The differential diagnosis includes autoimnrnne hepatitis and Wilson's disease (a-1
antitrypsin deficiency/chronic hepatitis infections should also be considered).
Additionally, it is in1portant to note whether there is a family history of autoirmnune
0, disease.
:::,
0.
Other factors which should be sought from the history include the medical history of
)>
:::, the patient, any drug history, a history of deteriorating school performance, etc., and
any exposure to i.v. blood or blood products.
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(1)
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Further investigations may include:
-+,
0
� Hepatitis serology
r+
:::r For Wilson's disease:
slit lamp examination for Kaiser-Fleischer rings
(1)
z
(1) • plasma caeruloplasrn.in
• urinary copper before and after a penicillamine challenge
,,
0 e liver biopsy with measurem.ent of liver copper concentration
3 For autoimmune hepatitis:
0,
r+ • auto-antibodies including antinuclear antibody (ANA)
m • anti-smooth muscle (SMA) and anti-liver-kidney microsomal antibody (LKM-1)
><
0,
serum immunoglobulins
3 liver biopsy
To exclude a-1 antitrypsin deficiency and chronic hepatitis viral infection:
• a-1 antitrypsin level and phenotype
It is important to monitor patients for development of acute liver failure. A rising
bilirubin, an increasing prothrombin time and a falling serum albumin may all indicate
failing liver function and the need for possible transplantation.
The most common causes for chronic liver disease presenting in previously healthy
older children are autoimmune hepatitis and Wilson's disease. Differentiating between
the two conditions can be difficult.
In autoirmnune hepatitis, there is a 75% female preponderance, 20% have another
autoimmune disease and 40% have a history of autoimmune disease in a first-degree
relative. The aminotransferases are variably raised but the alkaline phosphatase tends to
be normal. Type 1 characteristically has ANA and SMA positivity and type 2 has
LKM-1 positivity. The diagnosis also depends on excluding other disorders, especially
Wilson's disease. If coagulation allows, a liver biopsy should be performed to aid both
diagnosis and assessment of the degree of inflammation and fibrosis. Cirrhosis is present
in -70% at diagnosis. Recurrence of the disease occurs in approximately 25% after
transplantation.
202
CASE 5.1..-8
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Fig 5.18
A 12-year-old girl, recently diagnosed with Crohn's disease had been commenced
on appropriate treatment and, at outpatient review, her symptoms had improved.
However, 6 weeks later, she developed exquisitely painful lesions in both axillae. She
was given antibiotics with no improvement, and new lesions emerged on her arms and
shins as shown.
What are these lesions?
i. Kaposi's sarcoma
ii. Dermatitis herpetiformis
iii. Acanthosis nigrans
iv. Pyoderma gangrenosum
v. Erythema nodosum
vi. Necrobiosis lipoidica
203
ANSWER TO CASE 5.18
iv. Pyoderma gangrenosum

associa
t:J The lesions are pyoderma gangrenosum. The cause of this is not clear. Man\ 'disease,
C: tions wit!� systen�i� disease h�ve been describe� includi�� inflammatory boW: atien ts
ro
� _ _ fp
rheumatoid arthnt1s, leukaenua and chrome active hepat1t1s. Twenty per cent p od ern--ia
o· have a history of trauma. Up to one-third of cases have no systemic illn ess . y an
s a n1e
gangrenosum has the same prevalence in girls and boys, and in children �a [orrning
:::,
V,
age of onset of 10.2 years. The lesion often begins as a pustule which rup�ur�
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ern
a. ri p a tt
:::,
an ulcer with a mucopurulent base. They heal with a characteristic cri�iforr ear ances
of scarring. The most common site is the lower limbs. Histopathologic apP
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� vary and are usually not helpful in confinning the diagnosis. _
� onal
treat
V,
The managen1ent of pyoderma gangrenosum is difficult. Topical and intr al�si. unosup
--+, i
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d , a n
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204
CASE 5.19 ;;
a b
Fig 5.19
An 11-year-old girl was brought to hospital by ambulance. She had had 2 days of
abdominal pain, vomited twice, slight headache and mild fever. She had become
increasingly lethargic and slept during the day. When she awoke, she was confused, ot
disorientated and unable to move. She had no previous medical problems, and h3 nd ?
travelled abroad since a holiday to Greece a year before, from which she had reta ine
a suntan.
a
On examination, airway and breathing were normal, heart rate was 135 bpm, cap ill :{
refill was 4 s and blood pressure was 88/64 mmHg. GCS was 13 and temperature W
38.0 ° C. There were no localising signs of infection, including no meningism.
Fundoscopy was normal.
9
10 /I,
Investigations were as follows: Hb 14.8 g/dl, WBC 13.7 x 10 9/I, neutrophils 10. 3 )(
platelets 307 x 10 9/I, CRP 8 mg/I, Na 119 mmol/1, K 5.9 mmol/1, urea 6.6 mmol/1,
creatinine 70 mmol/1, Ca 2.46 mmol/1, ALP 234 mmol/1, glucose 2.0 mmol/1.
Cranial CT, and CSF pressure, chemistry and microscopy were normal.
right,
A full septic screen was performed. Figure 15.19.a and b show her hand (on the
next to her older sister's for comparison).
What is most likely diagnosis?
i. Addison's disease
ii. Waterhouse-Friederichson syndrome
iii. SIADH (syndrome of inappropriate ADH secretion)
iv. Water intoxication
v. Acute renal failure
vi. Cerebral infection (with associated salt wasting)
vii. Conn's syndrome
viii. Bartter syndrome
ANSWER TO CASE 5.19
L Addison's disease
D The hyponatraemia is striking. The differential diagnosis includ es the syndromes of
C
lD inappropriate antidiur etic hormone secretion or cerebral salt wasting (s�condary to
� intracranial infection), and water intoxication. However, the skin ta nrun ?. and the
6' hypoglycaemia suggest chronic adrenal failure and an A ddisonian crisis precipitated by
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an infecti on.
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a. C auses of acute adr enal insufficiency include adren al destruction, e.g. haernorrh age du e
)> to birth trauma and Waterhouse-Fridierichson syndrome (sepsis and collaps. e, of t� n
associated with meningococcaemia). However, acute causes would not give skm
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ro pigmentation.
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-+, In itial management involves circulato1y support \Vith fluid boluses a nd inotropes if
0
.... required, glucose, antibiotics for possible infection , and corticosteroids (with adequ ate
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-:::J'" sodium r epl acement , n1ineralocorticoids are not n eeded acutely).
l'D
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Synacthen test (this must w ait 12 h after a dose of hydrocortisone) results were as
� follows:
,,
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Cortisol at time
3
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0 min - 75 nmol/1
30 min - 85 nmol/1
ri-
m 60 min - 88 nmol/1
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ru The absence of a rise confirms Addison's disease.
3
Investigati ons for th e cause are also needed:
auto-antibodies
long-chain fatty acids (for adrenoleucodystrophy)
CXR
tuberculin test for tuberculosis
TB was the most co1111non cause of adrenal failure in the 1950s. Auto-imr:n.une failure
is now much more conunon. There are associations with other auto-imrr1une condi
tions including hypothyroidism., hypoparathyroidism, mucocutaneou s c andidi asis, d�a
betes mellitus, cirrhosis and alopecia, but the se can remain subclinical. LoW T4 with
raised TSH levels are common at presentation, but often correct rapidly with gluco
corticoid treatment without thyroxine. Auto-antibody tests could encomp,1.ss adr.enal,
thyroid, pituita1y gland, coeliac, gastric parietal cell, antinuclear antibody, li•ver micro
somal, smooth muscle and mitochondrial antibodies.
Treatment is \�rith hydrocortisone and fludroc ortisone. A mild androgenic prep aration
may improve libido and pubic hair growth in a dole scent and adult women, but puberty
is usually normal in timing and progression.
Other important aspects of long-term m anagement include a "Medic Alert'' bracelet ,
steroid card, information sheet and booklet about what to do when unwell in£ormation
to local A&E, and teaching the technique for emergency i.m. h;dro cortisone
inj ection .
5
CASE 5.20
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Fig 5.20.A Fig 5.20.B
This term baby was growth retarded at birth and had this skin lesion. The pregnancy
had been normal apart from maternal smoking.
What is the skin lesion shown?
i. Congenital scleroderma
ii. Staphylococcal infection
iii. Congenital CMV
iv. Epidermolysis bullosa
v. Aplasia cutis congenita
207
ANSWER TO CASE 5.20
v. Aplasia cutis congenita (ACC)
.0 Aplasia cutis congenita (ACC) is a rare disorder characterised by localised absence of

C
Cl) skin at birth. This baby had a large area of symmetric aplasia cutis congenita affecting
� the parietal scalp on both sides, both thighs, both scapular areas and a band running
o· across the midline of his back. This was treated conservatively with flamazine dressings,
:::s
VI
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followed by hydrocortisone 1 % over granulating areas and then sirnple jelonet and
:, gauze. Skin grafting ,vas not needed.
Cl.
)> In the classification of ACC as proposed by Frieden et al, type V is related to the
:::s
VI presence of a fetus papyraceous (see photo) or placental infarcts. In this case, the preg
� nancy was initially a t,vin pregnancy but one twin died at 11 weeks. The aetiology is
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VI
thought to be placental transfer of en1boli or thron1boplastic n1aterial through vascular
-+,
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� shunts. It is hypothesised that this precipitates DIC in the fetus, with a resultant hyper
,-+ coagulable state due to relative fetal antithrombin III deficiency. The skin defects are
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Cl) probably as a result of congenital vascular disruption secondary to embolisation. The
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reason for the characteristic syn1metrical distribution is not known.
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208
CASE 5.21
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Fig 5.21
A 4-month-old boy was brought to casualty. His grandmother had found him unwell
and "breathing funny" and called an ambulance. She said he was asleep when she
arrived to baby-sit whilst his mother went out. He had apparently taken a full feed just
before she arrived, but she found him unwell an hour later. Paramedics found him pale
and obtunded and had noticed facial twitching.
On examination, he was pale and drowsy with a capillary refill time of 3 s and oxygen
saturation of 88%. He was resuscitated and stabilised. Examination of his fundus was
as shown and additional investigations gave the following results:
. Hb 8.8 g/dl
WBC 22.4 x 109/I (neutrophils 30%, lymphocytes 68%, monocytes 2%)
platelets 780 x 109/1
CRP 86 mg/I
blood sugar 7.1 mmol/I
CSF examination - blood stained CSF (protein 0.64 mg/I, sugar 3.2 mmol/I)
CSF microscopy (WBC 3/mm3, RBC 1600/mm3, no organisms seen)
i. Meningococcal meningitis
ii. Herpes encephalitis
iii. Inflicted head injury
iv. Aspiration pneumonia
v. Urinary tract infection
b. Which one of the following is not necessary once the baby is stabilised?
i. Skeletal survey
ii. Coagulation screen
iii. CT head
iv. CT thorax
v. Examination of siblings
vi. Involvement of social services
209
ANSWERS CASE 5.21
a. iii. Inflicted head injury
b. iv. CT thorax
t:)
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(I) Inflicted head injury is an acute paediatric and neurosurgical emergency. Retinal haem
� orrhages are characteristically present, and ophthalmic examination is essential in any
o· acutely unwell young child. The first priority is to resuscitate, stabilise and make
:,
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appropriate referrals. Until the diagnosis is confirmed the baby should have a full septic
:J screen and be treated with i.v. antibiotics. The parents should be contacted and inter
a.
viewed. Associated injuries may include skull fractures, rib fractures and metaphyseal
)>
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fractures of long bones. This type of abuse may be associated with a family under great
� stress, and other siblings need paediatric evaluation. Inflicted head injury carries signifi
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cant mortality and morbidity, and clinicians should consider this possibility in all sick
-h small infants with sudden neurological deterioration.
0
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r+ Further steps that may be required include care of airway and breathing possibly involv
=r
m ing an anaesthetist; volume replacement, initially human albumin or plasma followed
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by a blood transfusion if necessary (clotting screen prior to transfusion). Urgent transfer
to a paediatric intensive care unit should be considered. A thorough external examina
,,0� tion for other signs suggestive of non-accidental injury should be performed, and an
3
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urgent CT scan of the brain with neurosurgical involvement as indicated. CT might
reveal subdural haematomas, cerebral oedema, contusions, intracerebral haemorrhage,
r+
m midline shift and acute hydrocephalus depending on timing and severity of injury.
><
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3 repeating after 2 weeks (a single X-ray does not exclude injury). This might reveal
skull fractures, rib fractures and metaphyseal fractures of long bones depending on
timing and severity of injury. In some units bone scans are no longer routinely recom
mended in cases of child abuse.
There nrnst be urgent contact with the parents to explain the situation, and early
involvement of the child protection team. Arrangements need to be made with social
services for evaluation of siblings, and moving to a place of safety if necessary.
The prognosis of these babies is very variable. Many will suffer long-term disability.
Those most affected may show severe learning difficulties, cerebral atrophy and micro
cephaly, visual impairment, seizure disorders or cerebral palsy.
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Fig 5.22.A Fig 5.22.B
A baby girl was born at 30 weeks' gestation following prolonged rupture of the
membranes from 25 weeks' gestation. She was in good condition at birth and
developed no respiratory distress. She was noted to have an asymmetrical facial
appearance and on closer inspection was found to have an epibulbar dermoid.
i. CHARGE association
iii. Treacher-Collins syndrome
iv. Klippel-Feil abnormality
v. Goldenhar syndrome
vi. Pierre-Robin sequence
211
ANSWER TO CASE 5.22
v. Goldenhar syndrome
0 The photo shows a nasogastric tube in situ, an abnormal left ear, hypoplasia of the left
C:
(I) side of the face, and a left facial nerve palsy. Closer inspection of the eye revealed an
� epibulbar dermoid.
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VI Hemifacial m.icrosomia, facio-auriculo-vertebral spectrum and Goldenhar syndrome are
llJ
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often used synonymously to describe this constellation of disorders affecting the jaw,
a. mouth and ear unilaterally. Abnormalities of the eye (characteristically epibulbar der
)> moids) and vertebrae also occur. It generally occurs sporadically, although autosomal
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CASE 5.23
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Fig 5.23
A 14-day-old baby was referred by his GP with a history of poor feeding and vomiting.
He had been born at term following a normal pregnancy, weighing 3700 g. He was the
first child of young parents. On examination, he weighed 3400 g and was lethargic and
approximately 5% dehydrated. He was jaundiced and had oral and perinea! candidiasis.
His pulse was 150, BP 88/40. The appearance of his genitalia is shown. His initial
electrolytes showed:
Na 115 mmol/I
[
K 6.7 mmol/I
Urea 11.8 mmol/I
Creatinine 117 mmol/I
Glucose 4.8 mmol/I
a. What i(�required in the immediate management?
i. i.v. fluid rehydration with normal saline
ii. i.v. fludrocortisone
iii. i.v. hydrocortisone
iv. Regular blood glucose and blood pressure measurement
v. Regular electrolyte measurements (4-6 hourly)
b. What investigations will confirm the diagnosis?
i. Synacthen test
ii. 21-hydroxyprogesterone (21-OHP)
iii. 17-hydroxyprogesterone (17-OHP)
iv. Renin
v. Cholesterol
213
a. ii. i.v. fludrocortisone
b. iii. 17-hydroxyprogesterone (17-0HP)
,0 iv. Renin
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The likely diagnosis here is congenital adrenal hyperplasia (CAH). This baby has pre
sented in a salt-losing crisis, he has a rugose, pign1ented scrotum and a large phallus,
VI
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all consistent with a diagnosis of CAH. Classical CAH is due to a deficiency of the
:::s adrenal steroid 21-hydroxylase enzyme in 90% of cases. Affected female infants may
Q..
be born with genital ambiguity of varying degrees; however, males have normal exter
)>
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VI
nal genitalia and the diagnosis may not be obvious at birth. Those with deficient
aldosterone production may therefore present with renal salt wasting and plasma volume
ro
...,
VI
loss with hyperkalaemia, which can lead to vascular collapse, shock and death. Dehy
-h dration from salt loss may occur as early as weeks 1-4 of life and this occurs in up to
0
..., 75% of all cases of classical CAH. Those who do not present with a salt wasting crisis
,-+
::::; may present later with progressive virilisation.
ro
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In classical 21-OH deficiency, baseline 17-OHP concentrations are diagnostic, and
� renin will be elevated. Urinary steroid profiles should also be checked which will
'Tl demonstrate the level of the enzyme block in the other forms of CAH.
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Fig 5.24
A 12-year-old girl was referred to the hospital by her GP with a widespread blistering
rash. There was a 2-week history of cough and flu-like symptoms which had been
treated with amoxycillin. The rash, which was itchy, started on her hands and then
spread to the axillae, thighs, buttocks and arms. On examination, she was apyrexial,
with a rash, but otherwise well. The rash was also present in her mouth and on her
genitalia, palms and soles.
The girl was reviewed by the dermatologist who suggested two investigations as new
crops of blisters continued to appear over the next few days.
On obtaining the results of the investigations, the dermatologist recommended
treatment with dapsone or sulphamethoxypyridazine.
What do you think was the final diagnosis?
i. Bullous pemphigoid
ii. Chronic bullous disease of childhood
iii. Staphylococcal scalded skin syndrome (SSSS)
iv. Herpes simplex type 2
v. Epidermolysis bullosa type II
vi. Hand, foot and mouth disease
215
ANSWER TO CASE 5.24
ii. Chronic bullous disease of childhood
.0 Differential diagnoses of a bullous eruption should include:

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Erythema multiforme (Stevens-Johnson syndrome)
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(I)
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Generalized herpes simplex
Chronic bullous disease of childhood (linear IgA disease).
VI
a, It is important to send blister fluid to virology for electron microscopy from any bullous
a.
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or vesicular eruption. The dermatologists may also perform a skin biopsy (for
)> immunofluorescence).
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VI
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Chronic bullous disease of childhood is an acquired, probably autoimmune, disease
....
VI
with involvement of skin and mucous membranes. The single most important investi
-+, gation is a biopsy of uninvolved skin which shows subepidermal blisters characterised
0
.... by IgA antibodies reacting with the basement membrane zone of the skin which is
,-+
::::r detected by direct immunofluorescence. There is no definitive treatment for this condi
ro
tion, and therapy is aimed at controlling the disease. In our patient, dapsone was not
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is a known side-effect of the drug.
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In approximately 65% of children, the disease goes into remission but in others it may
persist into adult life.
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216
r
A 6-week-old boy is referred to clinic because of floppiness. He was born at term by
spontaneous vaginal delivery. Examination reveals dysmorphic facial features, �
hepatomegaly and extensive generalised hypotonia. His cardiovascular and respiratory ::0
("')
examination is normal. -0
("')
I
Results of metabolic investigations are: -0
Blood lactate 7 mmol/1 OJ
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Arterial blood gas normal N
Organic and amino acids normal
Piperocolic acid marginally raised
Serum ammonia 80 µmol/1
Serum glucose 2.5 mmol/1
VLCFA increased
Phytanic acid raised
Dihydroxyacetone phosphate acyl transferase decreased
a. What diagnosis do these results infer?
i. Biotinidase deficiency
ii. Zellweger syndrome
iii. Urea cycle disorder
iv. Moebius syndrome
b. Choose three associated features of this condition:
i. Cleft palate
ii. Neonatal hypoglycaemia
iii. Large anterior fontanelle
iv. Talipes equinovarus
v. Patent ductus arteriosus
vi. Absent corpus callosum
vii. Retinopathy
viii. Syndactyly
ix. Deafness
219
ANSWERS TO CASE 6.1
a. ii. Zellweger syndrome
b. iii. Large anterior fontanelle
vii. Retinopathy
ix. Deafness
This baby has Zellweger syndrome. This is one of a group of 17 peroxison1al disorders.
QJ
Others include infantile Refsrnn and neonatal adrenoleukodystrophy. All of them
:::i present in a similar fashion and the absolute diagnosis depends on biochen1ical analysis.
a..
The cardinal features are facial dysmorphism including paucity of facial movements,
)>
:::i large anterior fontanelle, pr01ninent forehead, broad nasal root and hypoplastic supraor
bital ridges; hepaton1egaly (80%); prenatal renal cortical cysts (70%); congenital sensori
....
(I)
V,
neural hearing impairn1ent (90%); cataracts (70%); peripheral pigmentary retinopathy
-+, (40%); optic nerve hypoplasia (40%); calcific stippling of the patellae and synchondrosis
....
0
of the acetabulmn.
,-+
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(I) Diagnosis is by electroretinogram (abnormal in 85%), brainstern_ auditory evoked poten
z
(I)
tials and skeletal survey. Biochemical abnonnalities are increased saturated VLCFA.
C26:0 1nay be 5 times normal (0.33 mcg/ml). In addition, ratios of C24:0/C22:0 and
,,
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C26:0/C22:0 are raised. Many gene nrntations have been identified that cause abnor
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n1alities in peroxisome assen1bly and function.
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220
You are asked to see a 24-hour-old male infant on the postnatal ward because he has
small spots all over his body. He is feeding well and appears otherwise completely
healthy.
On examination he has petechial spots over his face, trunk and limbs. He has no
organomegaly or lymphadenopathy and the rest of the examination is normal.
FBe showed: Hb 15.7 g/dl, wee 12.0 x 109/I and platelets 10 x 10 9/1.
i Maternal idiopathic thrombocytopaenic purpura
<asabach-Merritt syndrome
iii. Congenital leukaemia
iv. Congenital rubella
v Alloimmune thrombocytopaenic purpura
vi. Traumatic petechiae
vii. Maternal anticonvulsant therapy
221
6.2
i. Maternal idiopathic thrombocytopaenic purpura
v. Alloimmune thrombocytopaenic purpura
0
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(1) Investigations should include checking the maternal platelet count and maternal
�
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antiplatelet antibodies.
V, Isolated thrombocytopaenia in the neonate is usually related to transplacental IgG from_
Ill the n1other.
:::,
D...
Neonatal alloimmune thron1bocytopaenia (NAIT) is similar to haernolytic disease of
)>
:::,
V, the newborn, with maternal antibodies crossing the placenta to destroy fetal cells.
NAIT is caused by maternal antibodies directed against fetal platelet antigens, inherited
....
(I)
V, from the father, which cross and enter the fetal circulation. These antibody-covered
-
0
.... platelets in the fetus or in the neonate are destroyed at an increased rate, leading to
,-+ thrombocytopaenia and petechiae.
::::;
(1)
Human platelet antigen-la (HPA-la, formerly known as PLAI) is the most common
z
(I) antigen found in over 75% of cases.
�
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NAIT with platelet counts <50 000/µl occurs in about 1 : 1000 births.
3
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Managen1ent involves daily platelet counts and platelet transfusions if levels fall below
,-+ 20-30 000/µl or if there is significant bleeding. Babies should be closely monitored for
m external and internal bleeding such as intracranial haen1orrhage. The natural history of
><
Ill NAIT is that the thrombocytopaenia usually resolves within 3-4 weeks but can last up
3 to 3 n10nths. It is important that parents are counselled regarding future pregnancies.
Autoimnmne neonatal thrombocytopaenia is usually seen in babies whose mothers have
a history of idiopathic thron1bocytopaenic purpura (ITP).
222
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Fig 6.3
A 2-month-old baby boy was presented to casualty, collapsed. His mother's pregnancy
had been normal, as was his birth. The examination after his resuscitation was normal.
He was admitted to the paediatric intensive care unit. Extensive investigations at the
time were normal. He was easy to ventilate and quickly weaned from the ventilator.
The following night he collapsed on the ward and required reventilating. An arterial
blood gas 1 h after reventilating showed: pH 7 .35, PO2 13.0 kPa, PCO2 5.9 kPa and
base excess 3.7 mmol/I. The sleep study is shown. When he was not ventilated an early
morning capillary gas showed a raised PCO2 .
i. Congenital myasthenia gravis
ii. Congenital cystic adenomatoid malformation of the lung
iii. Pulmonary hypertension
iv. Bronchopulmonary dysplasia
v. Duchenne muscular dystrophy
vi.:Ondine's curse
223
TO CASE
vi. Ondine's curse
Diagnoses which rnust be considered when he deteriorates on weaning from the ven
tilator include partially treated sepsis, seizure, arrhythmia, inborn error of metabolism
or a disorder of breathing control, e.g. Ondine's curse, also known as idiopathic con
genital central hypoventilation syndrome (CCHS).
QJ
::,
Investigations should include an early morning blood gas off the ventilator, 12-lead
a.. ECG, cranial imaging and a sleep study. Other investigations to be considered include
)> bronchoscopy, ophthalmological opinion, echocardiogram and muscle biopsy.
::,
The ease of ventilation and the dramatic response on two occasions in this case make
�
VI
the diagnosis of CCHS most likely.
-h
0
� This is confirmed by the sleep study - the chest and abdominal bands show a variable
,-+ respiratory effort. When the effort is poor there is hypoxia and hypercarbia.
:::;
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CCHS (Ondine's curse) is rare. It is the CO2 level during or prior to the collapse that
z
ro is important. This could be measured on a blood gas at the tin1e or by a formal sleep
�
.,,
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study. A typical sleep study in CCHS shows episodes of hypoxia associated with hyper
carbia and decreased chest and abdominal wall movement. The management of CCHS
3 is lifelong overnight ventilation. CCHS is associated with Hirschsprung's disease, oph
QJ
,-+ thalmological problems, ganglioneuroma, neuroblastoma, oesophageal dysmotility and
m heart rate variability.
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224
An 8-year-old child was referred by his GP with a 6-week history of lethargy, secondary
nocturnal enuresis, thirst and occasional vomiting. He showed normal growth and
examination was unremarkable apart from possible pigmentation of his knuckles and
umbilicus.
Initial investigations by the GP gave the following results:
Hb 14.5 g/dl
Na 131 mmol/I
K 5.3 mmol/I
Urea 11.1 mmol/I
Glucose 3.4 mmol/I
Thyroid function normal
Random cortisol 276 nmol/I (120-400)
a. What is the most likely diagnosis and what test would you do to confirm
the diagnosis?
a. Hypopituitarism 1. Chromosomes
b. Noonan syndrome 2. Echocardiogram
c. Cushing's syndrome 3� Short synacthen test
d. Kallman's syndrome 4. Cerebral MRI
e. Addison's disease 5. Insulin tolerance test
b. If this child had been found to have a low serum calcium, what other
diagnosis would need to be considered?
1. Hypercalcaemia
i 1. Hypophosphatasia
iii. Hypoparathyroidism
iv. Pseudohypoparathyroidism (PHP)
v. Vitamin D dependent rickets
225
a. e. and 3. Addison's disease and short synacthen test
b. iii. Hypoparathyroidism
D
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(I)
This child has Addison's disease (autoimmune adrenal failure), which can be confirmed
V,
o· by a short synacthen test. This ,vas abnormal in the child showing a basal cortisol level
r+
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of 180 nmol/1 with no response to stimulation. Random cortisol levels are unhelpful
V,
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in this situation as an elevated ACTH may maintain them in the nonnal range
::i initially.
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)> The diagnosis can be confirmed by the presence of anti-adrenal cytoplasmic

::i
V, antibodies.
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If there was associated hypocalcaemia found, type I autoinmrnne polyendocrinopathy
- also needs to be considered. In this disorder, hypoparathyroidism precedes the develop
0
.... n1ent of Addison's disease and is also associated ,vith mucocutaneous candidiasis.
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226
A 20-month-old boy was scalded by hot coffee spilling onto his upper chest, causing a
3% body surface burn. A&E staff assessed the burn as mainly superficial partial �
thickness. He was treated with simple analgesia and a silicone-gauze dressing and ;,:,
()
discharged. The following day he developed a fever, diarrhoea and vomiting. That '"Cl
()
evening he attended his local GP out-of-hours service and was referred to hospital. At I
triage his pulse was 165 bpm, respiratory rate 36/min and blood pressure '"Cl
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100/65 mm Hg; he had a temperature of 39.1 °C. He was pale, drowsy, with mild ;::i
clinical dehydration but no rash, focal neurological signs or neck stiffness. His burn N
looked clean with no sign of cellulitis. Initial laboratory studies showed a WBC of 5.2 x
109/I, platelet count of 232 x 109/I and normal plasma glucose. U&Es supported mild
dehydration: Na 132 mmol/I, K 2.5 mmol/I, urea 12 mmol/1. He was started on i.v.
fluids. He developed progressive circulatory failure, reduced urine output and a high
fever. His WBC rose to 25 x 109/I, platelets fell to 83 x 109/I, and he developed a
coagulopathy. His U&Es showed marked worsening of his hyponatraemia, hypokalaemia
and uraemia, and LFTs became abnormal.
i Staphylococcal scalded skin syndrome
ii. Toxic shock syndrome
l<awasaki syndrome
Toxic epidermal necrolysis
Stevens-Johnson syndrome
vi. Necrotising fasciitis
227
ANSWER TO CASE 6.5
ii. Toxic shock syndrome (TSS)
0 This is a potentially life-threatening exotoxin-n1ediated disease caused by Staphylococcus

C
0)
aure11s or Streptococcus pyogenes. The staphylococcal exotoxin, toxic shock syndrome
� toxin-1 (TSST-1), diffuses into the blood and causes the illness in the absence of tissue
o· invasion by staphylococci. Low or absent levels of antiTSST-1 antibodies may indicate
:::s
VI
OJ susceptibility to the illness. Management involves intensive care with aggressive fluid
:::s resuscitation, i.v. antibiotic therapy (cefotaxime and flucloxacillin), vasopressors and
0..
immunoglobulin therapy. TSS is an uncommon but well-established complication of
)>
:::s even relatively minor burns in children. In most cases there is a prodromal period with
�
0)
fever (>38. 9 ° C), myalgia, headache, vomiting and diarrhoea before the onset of hypo
.....
VI
tension and nrnltiorgan failure. A generalised macular erythen1atous rash develops after
- a few days. In the recovery phase there is desquan1ation of the paln1s and soles, fingers
0
..... and toes. Parents should be advised to seek professional advice if their child develops
r-+
::S a feverish illness after a burn injury.
O)
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228
Fig 6.6
A 6-year-old girl presented with a low-grade pyrexia, poor appetite, painful elbows and
ankles, abdominal pain and diarrhoea. On examination, she had flushed cheeks, a
papular itchy rash on her right arm, an ejection systolic murmur and minimal swelling
and tenderness of the affected ankle joints. She failed to improve with her initial
management but on day 3 developed a characteristic rash. She also had blood and
protein in her urine and had developed mild hypertension. She began to improve
spontaneously over the next few days but subsequently went on to develop some
uncommon but serious complications of this illness (see Fig. 6.6).
a. What conditions would you include in your initial differential diagnosis?
SELECT THREE APPROPRIATE ANSWERS
i. Scarlet fever
ii. Henoch-Schonlein purpura
iii. Nephrotic syndrome
iv. Rheumatic fever
v. Lyme disease
vi. Kawasaki's disease
vii. Vasculitis
viii. Systemic juvenile chronic arthritis
ix. Measles
x. Subacute bacterial endocarditis
b. The scan illustrates an extremely rare complication of this condition. What
does it show?
i. Cerebral haematoma
ii. Cerebral abscess
iii. Cerebral tumour
iv. Meningitis
229
a. ii. Henoch-Schonlein purpura (HSP)
iv. Rheumatic fever
D viii. Systemic juvenile chronic arthritis
C
(D
� b. i. Cerebral haematoma
o·
::) Initial differential diagnosis should include bacterial sepsis, viral infection, rheuniatic
VI
OJ
fever, Henoch-Schonlein purpura, syste1nic juvenile chronic arthritis. By day three the
::) diagnosis of Henoch-Scbonlein purpura should have been made.
a..
)> The MRI scan shows a large right fronto-parietal haematoma surrounded by
::)
oedema.
�
(D
""I
VI
Sixty per cent of children with HSP will have son1e degree of nephritis, from micro
-h scopic haematuria to a full-blown nephritic picture. Those that need nephrology
0
""I follow-up include those ,vith persistent moderate proteinuria, those who present with
r+
:::r an acute nephritic or nephritic-nephrotic picture, or those with progressive renal
(I)
impairment.
z
(I)
� Of those ,vith microscopic haematuria only, almost 100% are likely to have nonnal
.,,
0
GFR and BP at 10 years. In contrast, of those who are nephritic, 40% will have end
3
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stage renal disease at 10 years and only 20% will have normal renal function.
r+
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230
A 4-year-old presents to casualty with a limp. He is thought to have an irritable hip.
After a normal hip X-ray, he is discharged. He continues to have intermittent hip and �
back pain and is seen by the GP who follows him up for anaemia. The anaemia fails to ;o
(")
respond to 4 weeks of haematinics and he is referred to the nearest hospital. He has a -0
(")
left-sided limp on admission and complains of pain in the right leg. His Hb is 7.5 g/dl. I
There are no other clinical findings. -0
n,
;::i
What investigations would you do next? N
SELECT FOUR ANSWERS ONLY
i. Repeat hip X-ray
ii. fVIRI hip
iii. FBC and film
iv. Erythrocyte sedimentation rate
v. CXR
vi. Left knee X-ray
vii. X-ray lumbar spine
viii. fVIRI spine
ix. Bone scan
x. Skeletal survey
x1. B 12 and folate
xii. Bone marrow aspiraton
On reviewing the first X-ray, there is a small lytic lesion in the femoral head.
What differentials would you initially consider?
Haemophagocytic lymphohistiocytosis
Osteomyelitis
1ii. Histiocytosis
Avascular necrosis
Astrocytoma
vi. Neuroblastoma
vii Slipped upper femoral epiphysis
v111. McCune-Albright syndrome
1x. Albright's hereditary osteodystrophy
x. Collapsed congenital bone cyst
231
TO CASE 6.7
a. i. Repeat hip X-ray
iii. FBC and film
iv. Erythrocyte sedimentation rate
v. CXR
b. ii. Osteomyelitis
iii. Histiocytosis
OJ vi. Neuroblastoma
c..
:::;
History of pain in a child should always be regarded with caution, particularly persistent
)>
::,
V,
and localised. Backache is never normal in a child. Failure to respond to haematinics
(for anaemia) raised questions of aetiology. History should include bleeding tendency,
-i
V,
fever or sweating, loss of weight and diarrhoea. FBC, differential and blood film, and
-h CRP /ESR should be checked. Blood cultures, CXR and a repeat hip X-ray should
0
-i be done. Differentials of lytic bone lesions include osteomyelitis, histiocytosis, giant cell
r+
:::, tumour, malignant tumours, neuroblastoma, peripheral primitive neuroectodermal
(I)
turnour, and Ewing's sarcoma. Abdominal USS revealed a large, clinically non-palpable,
z
(I) retroperitoneal mass. AXR revealed widespread calcification. CXR was normal. Urine
catecholamines were n1.arkedly raised. A CT scan confirmed the mass and its extension:
-n
0 invasion of the bone marrmv with tumour cells. A diagnostic biopsy showed neuro
3
OJ
blastoma. Bone scan and MIBG revealed extensive bone metastases.
r+
m Neuroblastoma has myriad modalities of presentation. It can arise from any site along
>< the sympathetic nervous chain. Tumours may arise in the abdomen, adrenals, thoracic
OJ
3 or cervical areas. Metastatic extension is lymphatic and haematogenous. The latter

invades the bone marrow and results in anaemia. Bone metastases cause pain and lead
to limping in young children. Due to the type of catecholamine metabolites released,
hypertension is uncommon. Spontaneous bleeding into these tumours n1ay herald
severe abdominal pain. High thoracic and cervical masses can be associated with
Horner's syndrome, superior vena cava syndrorne and cord compression. Retrobulbar
and orbital infiltration vvith tumour may result in proptosis and periorbital ecchymoses.
Skin involven1.ent is exclusive to infants and presents as non-tender bluish subcutaneous
nodules. Paraneoplastic syndrornes associated with neuroblaston1a include opsomyo
clonus or cerebellar ataxia, and intractable secretory diarrhoea associated with hypoka
laernia and dehydration.
232
A 13-year-old girl has been diagnosed with Turner's syndrome following investigations
into her short stature and mild learning difficulties. She is below the 0.4th centile for
height on a normal growth chart and on the 75 th centile on a Turner's growth chart.
Initial investigations reveal normal thyroid function, antigliadin screen, serum urea and
electrolytes, bone profile, haemoglobin A 1C, cholesterol and triglycerides, with
markedly elevated gonadotrophin levels, low oestradiol and very small ovaries on pelvic '"ti
DJ
ultrasound. Her growth velocity is 1.5 cm/year giving a projected adult height of ""I
r+
145 cm (4' 9"), so growth hormone therapy is commenced with the intention to N
introduce oestrogen therapy later. One month after starting therapy, she develops
intermittent right-sided frontal headache lasting 1-2 min with blurring of her vision. Her
optic discs are swollen, visual fields are full to confrontation and neurological
examination is unremarkable. A CT brain scan is normal. A lumbar puncture is
performed with the following CSF results:
cytospin no cells seen
protein 0.27 g/I
glucose 3 mmol/I
microscopy 3 RBC and O WBC/HPF
opening pressure 22 cmH2 O
i. Venous sinus thrombosis
ii. Leukaemia
iii. Benign intracranial hypertension
iv. Hypoparathyroidism
v. Space-occupying lesion
vi. Viral encephalitis
233
iii. Benign intracranial hypertension
0 This girl has developed benign intracranial hypertension. This can be idiopathic but is
C also reported as a rare side-effect of grmvth hormone (GH) therapy.
(J)
Vl
r+
i5 At the time of the lumbar puncture, CSF should be drained until the CSF opening
::::i
Vl pressure is normal for her age (approximately 15 cm_ H2 0). GH therapy should be
OJ
::::i
discontinued. Benign intracranial hypertension is not a "benign" condition and the
Q. patient is at risk of visual deterioration and eventual blindness -without appropriate
)> management. Treatrnent is with acetazolan1ide, regular monitoring of serum potassium
::::i
levels and supplementation as required. Treatment needs careful co-ordination with
� ophthaln10logical review. If headaches persist and eye signs do not improve, fortnightly
...,
(J)
V,
lumbar punctures and steroid therapy may be necessary or in �ome cases a shunt
-I-,
0
..., procedure.
r+
:::r Other diagnoses -which need to be excluded include:
(D
connective tissue diseases, e.g. systen1ic lupus erythematosus
z
(D leukaemia
�
,,
0
venous sinus thrombosis, especially ,,rith otitis media or sinusitis (Gradenigo's
syndrome).
3OJ endocrine problems, such as diabetes mellitis, hyperadrenalism, hyperthyroidism and
,-+ hypoparathyroidism (already considered in this case)
m
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3
234
Fig 6.9.1
An 8-month-old baby boy presented initially with clustered episodes (over 2-3 min,
several times a day) of right-sided twitching of the face and body, with head and eye
deviation to the right. He was the firstborn twin (33 weeks' gestation by Caesarean
section for antepartum haemorrhage), Apgar scores for the twins were 7 and 9 at 1
and 5 min, respectively. Twin-to-twin transfusion was suspected antenatally and regular
scans were performed. Some amniotic fluid was drained from the amniotic sac of twin
1 on one occasion but no transfusions were given. His weight was on the 50 t h centile
(twin 2 on the 25th ) but he was not plethoric at birth. Both twins were admitted to the
neonatal unit after delivery and required oxygen therapy briefly. Developmental history
revealed that he smiled at 3 months, was cooing and laughing, reaching mostly with
the left hand but not yet rolling or sitting. On examination, his head circumference is
on the 50 th centile and weight on the 98th centile, he had slight head lag, subtle facial
asymmetry and a likely right visual field deficit. There was a paucity of movement on
the right side but no difference in tone or tendon reflexes. He subsequently developed
abnormal movements involving trunk flexion and extension of his upper limbs. An EEG
was obtained which showed chaotic and continuous abnormal background of very high
voltage with random slow waves and spikes.
i. Congenital toxoplasmosis infection
ii. Acute disseminated encephalomyelitis
iii. Cerebral palsy
iv. Hypoxic ischaemic encephalopathy
v. West's syndrome
vi. Rett's syndrome
b. What lesion is seen on the CT shown?
i. Anencephaly
ii. Left sided subdural haemorrhage
iii. Hydrancephaly
iv. Periventricular leukomalacia with left ventricular dilatation
v. Left porencephalic cyst
vi. Lissencephaly 235
ANSWERS TO CASE 6.9
a. v. West's syndrome
b. v. Left porencephalic cyst
D
C:
(I) This child has delayed 1notor milestones. Persistent head lag at this age is abnormal and
� he would be expected to be rolling, although not sitting. The clear hand preference
o· at this age is abnormal and indicates a right hemiparesis. The most likely diagnosis here
:::,
is West's syndrome with hypsarrhythn1ia on the EEG.

VI
QJ
a.
:::,
The CT shows a left porencephalic cyst, which has developed seconda1y to an infarct
)> in the territo1y of the right middle cerebral arte1y, occurring in the antenatal period.
:::,
VI A twin-to-twin transfusion was suspected in utero and the recipient would have been
�
(I) susceptible to vascular events, although this is more con11T10n when the donor twin
"""i
VI
has died in utero. Infarcts such as these also occur sporadically.
-+,
0
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236
A 17-year-old girl with Down's syndrome is seen for review at her school. She has
previously been healthy but required grommets as a young child because of conductive
hearing problems. Her parents are concerned that she had dropped two clothing sizes
s:
::,;:I
(")
over recent months; she was previously overweight. Her family and GP are aware that "."O
(")
she has missed some of her recommended health screens, particularly the blood tests, :c
because she is noncompliant with venepuncture. She is complaining of intermittent "."O
OJ
abdominal pain but there is no bowel or urinary disturbance. An abdominal ultrasound ;+
was normal, as was urinalysis. On examination, height is on the 5 th centile and weight N
on the 10th centile on the Down's syndrome growth chart. She has a slightly high
resting pulse rate and a short mid-systolic murmur heard at the mid/upper sternal edge
which did not radiate anywhere or vary in posture. Blood pressure was 100/70 mmHg.
Otherwise, examination was unremarkable. There is no relevant family history.
a. Which medical conditions are more prevalent in individuals with Down's
syndrome?
SELECT FIVE ANSWERS ONLY
i. Hyperthyroidism
ii. Hypothyroidism
iii. Sensorineural hearing loss
iv. Fallots tetralogy
v. Bronchiectasis
vi. Atrial fibrillation
vii. Asthma
viii. Crohn's disease
ix. Hypopituitarism
x. Scoliosis
Blood was sent for thyroid function with the following results:
Free T4 48.2
Free T3 12
TSH <0.02
Antithyroid peroxidase 390 K/1 (<32.0).
i. Grave's disease
ii. Congenital hypothyroidism
iii. Acquired hypothyroidism
iv. Hypopituitarism
v. Hashimoto's thyroiditis
237
TO 6.10
a. i. Hyperthyroidism
ii. Hypothyroidism
0 iii. Sensorineural hearing loss
C
� iv. Fallots tetralogy
(I)
a· X. Scoliosis
::;
Vl b. i. Grave's disease
ru
:::; The following conditions are more prevalent in Down's syndrome:
Q..
Cardiac: 40-60% of babies with Dovm's syndron1e have congenital heart disease and
)>
::; 50% of these have atria-ventricular septal defect. Other abnormalities that are n1ore
prevalent in these children include Fallot's tetralogy and various combinations of
(I)
""'I
Vl
VSD/ASD.
Orthopaedic: cervical spine instability, hip subluxation/dislocation, patellar instabil
ity, scoliosis, metatarsus varus and pes planus. Laxity of the transverse ligament of
r+
::r Cl or dysplasia of C1/C2 can predispose to dislocation or subluxation of the atlan
(I)
toaxial joint with potentially catastrophic con1plications. There are no screening
z
(I) methods to predict who of the Down's population is at risk. Sporting activities
�
.,,
0
should not be restricted if no clinical sympton1s are present. Particular attention is
needed when n1anipulating the neck of an unconscious child.
3
ru
Ears, nose and throat: >50% of children ,vith Dmvn's syndr01ne have hearing loss.
r+ Conductive losses are more common than sensorineural losses, and tend to persist
m into adolescence and adult life. Sensorineural losses, particularly presbyacusis, occur
><
ru more with advancing age. Upper airway obstruction and infection are also more
3 prevalent.
Ophthalmological: refractive errors occur in approximately 70%1 of individuals with
Down's syndrome. Congenital cataracts, nystagnms, squint, glaucorna, keratoconus,
blepharitis and blocked nasolacrimal ducts are also more common.
Endocrine: thyroid dysfunction, con1monly hypothyroidism and less comn10nly
hyperthyroidism is increasingly prevalent with advancing age. Uncon1pensated
hypothyroidism_ is found in 10% of patients of school age. Grmvth failure may arise
as a result of other chronic disease. Short stature is a feature of the condition and
adapted centile charts are available. Diabetes is also n10re con1mon.
GI: 10r,¼i of children ,vith Down's syndrome have congenital malformations such
as atresia of the jejunum_, duodenum, oesophagus and anus, annular pancreas
and exomphalos. Coeliac disease and Hirschsprungs disease are also more pre
valent; gastro-oesophageal reflux and oro-motor dysfunction can lead to feeding
difficulties.
Imrnunological: imnmnodeficiency and autoimnmne problems such as arthropathy,
vitiligo and alopecia are more c01nmon.
Haematological: transient neonatal 1nyeloproliferative states, leukaemia, neonatal
polycythaemia and thrombocytopenia may be seen.
Neuropsychiatric: infantile spasm_s, myoclonic epilepsies, autism and dementia (adults
only) are 1nore prevalent in this population.
The diagnosis here is Grave's disease. The management is initially carbimazole to render
her euthyroid and then replacement thyroxine as necessary. This is generally discon
tinued after about 6 months and if relapse occurs, definitive treat1nent with radioactive
iodine is given.
The following health checks are recommended by the UK Down's Syndron1e Medical
Interest Group:
Thyroid function: birth to 6 weeks (routine neonatal screen), then thyroid function
test including antibodies at 12 months, 3 years and then every second year or if
clinically indicated. Annual dried blood spot TSH n1easurement using fingerprick
blood may be available in son1e districts.
Growth: length, -weight and head circumference should be checked at any review
appointment during the first year and then annually. Down's-specific charts should
238 be used.
Eye check: check for visual behaviour and cataract at birth, visual behaviour and
squint at 6 and 12 months and from 2 years onwards, orthoptic examination, refrac
tion and ophthalmological assessment every second year throughout life or ,vhcn
clinically indicated.
Hearing: if locally available, neonatal screening should be arranged and full audio
s:
::::0
logical revinv (hearing, impedance, otoscopy) subsequently at 6 months, yearly until r,
7J
5 years and then every second year. r,
I
Cardiovascular assessment: full assessment including cchocardiograrn should ideally 7J
be arranged in the first 6 ,veeks. The possibility of acquired heart disease should be OJ
""<
r-t
considered at medical reviews for example secondary to upper airway obstruction. N
238A
Is it safe for a bottle-fed baby of 6 weeks to go swimming in the local
chlorinated leisure centre?
i. No, because the baby has not yet received any polio vaccine and risks contracting
poliomyelitis from a recently immunised child -0
ii. No, because the baby has not yet received a full course of polio vaccine and risks DJ
contracting poliomyelitis from a recently immunised child �
N
iii. No, because the baby has not yet received a full course of polio vaccine and risks
contracting vaccine-associated poliomyelitis from a recently immunised child
iv. Yes
239
1
iv. Yes
0 Yes in chlorinated pools, but until the child has received a full course of polio vaccine,
C
(J) not in seawater, as it may be contaminated with sewage. There is no risk of an unim
� munised child contracting vaccine-associated poliomyelitis from a recently immunised
o· child if they are taken swimming, so recently immunised children may be taken swim
:::i
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rning, even if they have been given oral polio vaccine.
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240
An 8-week-old baby girl presented to hospital with bruising. She had small bruises over
the left cheek, left lower back and left shin. The baby was an asylum seeker from
Eastern Europe, housed in a bed-sit shared with her mother, both maternal
grandparents and four maternal aunts/uncles with ages ranging from 2 to18 years.
There was no history of trauma. The baby was fully breast fed and the mother was
noted to be very thin. The baby weighed 3750 g (2nd centile). General examination was
unremarkable except for the bruises.
The baby was investigated with FBC, coagulation screen, U+Es, bone chemistry
and LFTs.
Blood results were as follows:
Hb 9.4 g/dl PT 18 s
WCC 11.1x10 9/I APTT 36 s
Platelets 466x10 9/I Fibrinogen 1.8 g/I
Total Ca 2.13 mmol/I Factor II 30% (34-102%)
Corrected Ca 2.23 mmol/I Factor VIII 107% (50-150%)
Phosphate 1.28 mmol/I Factor IX 13% (21-81%)
ALP 864 IU/I Factor X 30% (31-81%)
Bilirubin 18 µmol/I Factor XI 64% (50-150%)
ALT 27 IU/I
Total protein 52 g/I
What diagnoses are suggested by these results?
i. Hyperparathyroidism
ii. Non-accidental injury
iii. Vitamin D deficiency
iv. Hypoparathyroidism
v. Von Willebrand's disease
vi. Haemophilia B
vii. Vitamin K deficiency
241
iii. Vitamin D deficiency
vii. Vitamin K deficiency
D
C:
CD The history here raises the possibility of non-accidental injury (NAI). This should be
Vl
r+ considered in any infant presenting with unexplained bruising.
5·
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Vl A skeletal survey and ophthalmologic referral for fundoscopy should be performed
OJ
::;
routinely in any infant with a suspected NAI. Children under the age of one year
a.. should also have a CT head.
)>
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Vl
However, the results here den10nstrate vitamin K deficiency. Clotting factors II, VII,
�
CD
IX and X are vitarnin K dependent. Vitamin K deficiency results in a prolonged PT
""'I
Vl
and reduced assays of the dependent clotting factors. It is more con11T10n in breast-fed
- infants. It may present ,vith easy bruising. In this case, oral vitan1in K prophylaxis had
0
""'I been prescribed and dispensed, but was not given on account of con1munication
r+
::::; difficulties.
CD
z The biochemical results are consistent with a diagnosis of vita1nin D deficiency (rickets).
CD
� Vitamin D levels in the fully breast-fed infant are dependent upon the nutritional
""f1 state of the mother. In this case, the mother had nutritional vitamin D deficiency,
0
3
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accentuated by a reduction in exposure to sunlight. Vitamin D deficiency results in
a raised alkaline phosphatase, low calcium and a low normal phosphate level. This
r+
m baby had poorly mineralised bones on X-ray. Treatment is a course of alfacalcidol
>< 25-50 ng/kg.
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3
242
s:
:,.,
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N
FigG.13.1
A 12-year-old girl complaining of chronic shortness of breath, poor exercise tolerance,

and a long-standing cough productive of copious purulent sputum attends for a chest
radiograph, after which a CT of the chest is performed. At the age of 8 years, she had
a severe respiratory tract infection with pertussis. There was no other medical history of
note.
What is the likely pathology in the right lung?
i. Wegener's granulomatosis
ii Fibrosing alveolitis
iii. Bronchiectasis
iv. Legionnaire's disease
v. Congenital pulmonary hypoplasia
vi. Pneumocystis carinii pneumonia
vii. Pneumatocoeles
243
ANSWER
iii. Bronchiectasis
0 The chest radiograph demonstrates marked abnormality on the right with loss of
C
<D volume and widespread ring shadows seen predon1inantly in the mid and upper zones.
I.I\
o· The n1ediastinum is shifted to the right and there is more confluent shadowing at the
r+
:J right base which probably represents consolidation as evidenced by the multiple air
I.I\
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bronchograms seen. The left lung has herniated across the midline and appears to be
::i of large volume consistent with a degree of air trapping. No focal consolidation or
0..
ring shadows are seen on the left.
)>
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The CT confirms the abnormalities on the right where ring and tubular air spaces can
�
<D be seen. It is also noted that the right hemithorax is smaller than the left, consistent
'""'I
I.I\ with a long-standing process. On the left, the CT shows considerable "n1osaic attenu
-
0 ation" with the n1ore posterior aspect of the left lung being of markedly lower attenu
'""'I
r+ ation (i.e. darker) than the anterior aspect. In addition, the darker lung has nmch fewer
::,
<D vessels per unit area, adding to the lower attenuation.
z Given the history of chronic dyspnoea and a chronic productive cough, coupled with
<D
� the findings on both chest radiography and CT of ring and tubular shadowing and
,,
0
ongoing consolidation, the most likely diagnosis is bronchiectasis.
3
OJ
Bronchiectasis usually originates in childhood and can be defined as irreversible dilata
,-+ tion of the bronchial tree, usually localised. The definition includes the term irreversible
m
><
to exclude transient ainvay dilatation occasionally associated with pneurn.onia and atel
OJ ectasis. There are numerous causes for bronchiectasis, the commonest being postinfec
3 tious (including viral, pertussis, allergic bronchopulmonary aspergillosis and tuberculosis),
endoluminal bronchial obstruction (e.g. foreign body or mucoid im.paction, seen par
ticularly in patients with cystic fibrosis), ciliary dyskinesia (e.g. Kartagener syndrorn.e),
or secondary to longstanding immune comprom.ise (e.g. chronic granulomatous disease
of childhood). It is seen less nowadays than previously, due to improved antibiotic
therapy, vaccines against measles and pertussis, and more effective physiotherapy.
Postinfective bronchiectasis tends to be basally distributed in the lungs while that due
to cystic fibrosis or immune deficiency is usually upper zone in distribution. The chest
radiograph is occasionally normal in bronchiectasis (in approximately 7%, especially
early in the disease) but usually demonstrates abnormalities including crowding of the
bronchi, bronchial wall thickening, loss of definition of lung mark.ings due to peri
bronchial fibrosis, and lobar loss of volume, especially at the bases, with corn.pensatory
emphysem.a of the upper lobes. End-stage changes include ring and traniline shadows
(due to dilated bronchi seen end on and along their length, respectively) which can
give rise to a honeycomb appearance, as seen in the mid- and upper zones in this case.
Consolidation is a frequent complication, again as seen here. High-resolution CT
(1 nun slices, either 10 or 20 111111 apart) has become the radiological method of choice
for the investigation of suspected bronchiectasis, as it is very sensitive to dilated bronchi.
A bronchus should be of the same diameter as its accompanying pulmonary artery on
CT; if the bronchus is dilated, the so-called "signet ring" appearance is produced.
Other signs of bronchiectasis include the visualization of dilated bronchi more peripher
ally in the lung than usual, i.e. within 1 cm of the pleura. Cystic bronchiectasis may
demonstrate air-fluid levels within the dilated bronchi. Contrast bronchography is rarely
performed nowadays for the diagnosis of bronchiectasis but is occasionally used to
delineate the extent of disease if surgery is considered.
A mosaic attenuation pattern as seen in the left lung, due to a combinatio n of hypoper
fusion and hypoventilation, has a number of causes, including chronic thrornboembolic
disease and asthma. However, in the context of a previous severe chest infection, the rn.ost
likely underlying diagnosis is bronchiolitis obliterans. In this condition, endo- and peri
bronchiolar inflanunation causes distal airway occlusion. In the developing lung this
chronic hypoventilation gives rise to a decreased number of alveoli which are emphyse
matous, and hypoplasia of the pulrn.onary arteries supplying the affected segment, with
resulting hypope1fusion. Aside from previous infections (including pertussis, viral and
244 mycoplasma), other causes of bronchiolitis obliterans include toxic inhalation (ammonia
and phosgene), foreign body inhalation, chronic graft vs host disease and post heart-lung
transplant. A large percentage of cases, are, however, idiopathic.
A term neonate (3500 g) after an uneventful pregnancy and delivery, was found on the
post-natal ward to be cyanotic (at 8 hours of age). He was initially put on CPAP and s::
then ventilated. ;;::,
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Ventilation settings: ()
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CMV pressure 38/6, FiO 2 0.6 '"'O
SaO 2 50% 0,
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pH: 7.5
PaO 2: 3 kPa
PaCO 2 3 kPa
BE: 0
Normal 4-limb blood pressure
Normal perfusion
An umbilical arterial catheter (UAC) was inserted (12 cm) and bright red blood was
seen on drawing back the syringe. A CXR was done to check the position of the UAC,
showing mild patchy changes bilaterally; the tip of the UAC was the level of T6 aligned
to the left of the spine. It was therefore decided that the UAC had been inadvertently
inserted into the umbilical vein.
A blood gas sampled from the umbilical line showed: pH 7.55, pCO 2 2.5 kPa, pO 2
40 kPa
a. What are the most likely diagnoses?
i. Transposition of the great arteries
ii. Eisenmenger's syndrome
iii. Primary pulmonary hypertension
iv. Right-sided aberrant subclavian artery
v. Truncus arteriosus
b. What is the most appropriate investigation to confirm the diagnosis?
i. Nitrogen wash-out test
ii. Cardiac catheterisation
iii. CT scan
iv. Echocardiogram
245
TO CASE
a. i. Transposition of the great arteries
iii. Primary pulmonary hypertension
b. iv. Echocardiogram
An AXR and a CXR are needed to check the course and position of an umbilical
arterial catheter. In this case, it raised suspicion that a mere 12 cm "arterial catheter"
can reach the level of T6 in a term average weight baby. An abdominal film would
have demonstrated that the line did not go inferiorly to the iliac arte1y as an arterial
catheter would. Transducing the umbilical line would also help distinguish an arterial
and venous pressure trace.
These gas results show mcygenated blood from the UVC which is lying in the left
atrium. However, the radial sample is deoxygenated blood suggesting cyanotic
congenital heart disease. Differentials include transposition of the great arteries,
pulmona1y atresia, critical pulmona1y stenosis (with PFO or VSD), total anomalous
pulmonary venous congestion (obstructed type) and persistent fetal circulation (primary
puhnonary hypertension).
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246
A 6-year-old boy is admitted with a 5-day history of fever, lethargy, anorexia, jaundice
and dark urine. On examination he is pyrexial, pale, mildly icteric with
lymphadenopathy and tender hepatosplenomegaly. Initial investigations show:
Hb 5.5 g/dl
wee12.0 x 10 9/I (N 41%, L 47%, M 11%, atypical lymphocytes 1%)
Platelets 212 x 10 9/I
Bilirubin 37 µmol/I
Transaminases normal
Coagulation screen normal
i. Diamond-Blackfan anaemia
ii. Sickle cell anaemia
iii. Epstein-Barr infection
iv. Hepatitis A
v. Autoimmune haemolytic anaemia
vi. Weil's disease
b. Which specific complications should be considered?
SELECT TWO POSSIBLE ANSWERS
i. Splenic haemorrhage
ii. Severe haemolysis
iii. Cerebral abscess
iv. Cirrhosis
v. Overwhelming sepsis
247
ANSWERS TO 6.15
a. iii. Epstein-Barr infection
b. i. Splenic haemorrhage
ii. Severe haemolysis
The n1ost likely diagnosis is EBV infection (glandular fever/infectious n1ononucleosis)
,vith associated acute haemolysis.
Complications include severe haemolysis and splenic haen1orrhage. Neurological com
plications (e.g. seizures, ataxia, meningitis), airway obstruction (from_ tonsillar hypertro
phy) and hepatitis are among other problen1s associated with EBV infections but were
not apparent in this case.
Other investigations should include a monospot and EBV antibodies. An ultrasound
scan should be perforn1ed to exclude splenic haen1orrhage. Other causes of haen1olysis
should be considered especially if this boy is to be transfused.
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2,48
An otherwise healthy 2-year-old boy is referred by his GP with a 2-day history of
passing large dark, extremely offensive, non-mucousy stools. He has not had any
diarrhoea or constipation, and there is no history of vomiting. He has recently
complained of mild "tummy pain", but his appetite is unchanged and he has been able
to sleep at night. On direct enquiry, there are no other symptoms of note. On
examination, the youngster is pale and lethargic but alert. He is afebrile with a heart
rate of 140 bpm, blood pressure of 85/30 mm Hg, and respiratory rate of 24 per min.
The cardiovascular and respiratory systems are otherwise normal. He is tender
periumbilically, but there is no organomegaly, palpable mass, rebound or guarding.
Bowel sounds are reduced. The anal margin is normal.
lniti,:1i investigations reveal:
Hb 5.9 g/dl
CRP 6 g/I
wee 10.2 x 109/I
,ilbumin 36 g/I
platelets 158 x 10 9/I
I\Ja 138 mmol/I
ESR 22 mm/h
K 4.9 mmol/I
PT 13 s
Urea 13.6 mmol/I
APTT 32 s
ereatinine 43 µmol/I
Fibrinogen 1.9 g/I
An AXR is unremarkable.
i. Henoch-Schonlein purpura
ii. Arteriovenous malformation
iii. Von Willebrand's disease
iv, Meckel's diverticulum
v: lntussusception
vi. Ulcerative colitis
vii. Small bowel perforation
249
TO CASE 6.16
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3
This story is consistent with a diagnosis of Meckel's diverticulum with ectopic gastric
mucosa. This child presented with painless melaena, of which the n1ost common cause
at this age is bleeding associated with a Meckel's diverticulum. Intussusception is an
important differential diagnosis. Melaena or partially altered blood in the absence of
vomiting, significant abdominal pain, a palpable mass and with an unremarkable AXR
collectively mediates against the diagnosis of intussusception in this case. Other rare
causes of this presentation include upper gastrointestinal arteriovenous malformation
and duodenal ulceration. Meckel's diverticulum_ occurs in 2% of all infants, symptoms
usually presenting in the first 2 years of life. Acid secreted from_ ectopic mucosa lining
the diverticulurn causes ulceration of the normal adjacent ileal nmcosa with consequent
bleeding. A Meckel's diverticulum may act as a lead point for intussusception. Acute
diverticulitis 1nay mimic acute appendicitis.
Confirn1ation is n1ade with technetium_ scintigraphy. In a "Meckel's scan" (see Fig.
6.16), technetium is taken up by the mucus-secreting cells of the ectopic gastric
mucosa, facilitating visualisation of the diverticulum. The scan sensitivity is as high
as 85% when uptake is enhanced by cin1etidine or glucagon, and specificity is 95%.
Surgical excision is curative.
250
A 12-year-old girl is referred by her GP with the "peculiar problem of marked muscle
stiffness, pain, immobility and fatigue following exercise". She is otherwise quite well,
has not been missing school and is described as a keen athlete. In retrospect,
symptoms of post-exercise muscle fatigue date from the age of 6 years but have been
worse over the past year. There is no similar family history and the physical examination
proves to be normal.
a. What muscle disorder is the most likely cause?
i. Myasthenia gravis
ii. Myotonic dystrophy
iii. Fascio-scapulo-humeral dystrophy
iv. McArdle's disease
v. Polymyalgia rheumatica
vi. Fabry's di�ease
b. What further investigations would be relevant?
i. Anoxic exercise testing
ii. Gene analysis
iii. Tensilon test
iv. Muscle biopsy
v. Acute phase reactants
vi. Creatinine kinase
251
a. iv. McArdle's disease
b. i. Anoxic exercise testing
iv. Muscle biopsy
This girl has McArdle's disease. While several different disorders would need to be
considered, the presentation of fatigue with anaerobic exercise is most typical of Type
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V (McArdle) and Type VII (Tarui) glycogenoses and possibly one of the lipid myopa
:::i thies (carnitine pahnityl transferase deficiency).
Cl.
)> Investigations would include anoxic exercise testing using a blood pressure cuff, and
:::i
measuring lactate pre- and post-exercise (a failure of the blood lactate to rise would
be abnormal). A nrnscle biopsy ·would show increased glycogen and deficiency of
.....
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There is no definitive managern.ent, but advice on general lifestyle and the avoidance
,-+
:::; of strenuous exercise would be irn.portant.
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The prognosis is generally good, except for possible renal complications in adulthood
associated with n1.yoglobinuria.
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252
A survey of 6000 singleton deliveries was undertaken to investigate the association
between maternal smoking habits and the outcome of pregnancy. The following data
were produced:
Table 6.18.1
Perinatal deaths Survivors Births
Non-smokers 60 (a) 3940 (b) 4000

Ex-smokers 8 (c) 492 (d) 500
Smokers 39 (e) 1461 (f} 1500
Total 107 5893 6000
a. What is the overall perinatal mortality rate per 1000?

i. 107/5893
ii. 107/6000
iii. 107/5893 X 1000
iv. 107/6000 X 1000
b. What is the relative risk of perinatal death in the "smoking group" in
comparison to the non-smoking group?
e/(e +f)
i.
a/(a+b)
a/(e+f)
ii.
f /(a+b)
(e+f)/a
iii.
(a+b)/e
(e +f)/e
iv.
(a+b)/a
c. What statistical test could you use on this data to strengthen your
conclusion?
i. Paired t-test
ii. Chi-square
iii. Regression analysis
iv. Pearson correlation
v. Non-parametric regression
253
a. iv. 107/6000 X 1000
b. i. e/(e+f) 173
a/(a+b) =
C. ii. Chi-square
Mortality rate for deaths that occur close to birth is usually calculated by:
OJ No. of d�aths
::J 1000
c.. Total births x
)>
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"non-smoking" group is calculated by:
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-+, Perinatal mortality rate in the smoking group 3 /1000
0 9 1.73
""'I Perinatal mortality rate in the non-smoking group 60/ 4000
r-+
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(1)
The confidence interval is calculated from the relative risk. The 95% CI for this rela
z
(1) tive risk is 1.16-2.58. When interpreting the CI, we look to see if it contains 1, as
this is the value of the relative risk that would indicate that there was no statistically
-,,
0 significant difference between the risk in smoking mothers and non-smoking n10thers.
3
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This CI only contains values greater than 1, with the possibility of a relative risk as
high as 2.58. However, it is important not to over interpret this CI as the lower limit
r+
m
X
is very close to 1. In order to strengthen your conclusion, it would be useful to derive
OJ a p value for the null hypothesis; there is no difference in the risk of perinatal death
3 between mothers that sn1oke and mothers that don't smoke. An estimate for the p
value can be obtained by performing a Chi-square test on the data. The formula for
obtaining the Chi-square statistic is:
2 _ " (observed - expected/
X - Li expected
This statistic measures the discrepancy between the observed counts in the table and
the counts you would expect under the null hypothesis. For example, there were 99
deaths in total so if there were no differences between smoking and non-smoking
mothers, the expected nmnber of perinatal deaths to mothers that didn't smoke would
be:
4000
7
99x= 5500 = 2
The following 2 X 2 table illustrates the observed and expected values
Table 6.18.2
Died Survived
Observed Expected Observed Expected Total births
Mother didn't smoke 60 72 3940 3928 4000
Mother smoked 39 27 1461 1473 1500
Total 99 5401 5500
The figures in the above table are then entered into the formula for the Chi-square
statistic illustrated above. With reference to a table of Chi-square values, the calculated
value is greater than the tabulated value at a significance level of 1%, indicating p =
254 <0.01. Thus we have evidence to suggest that the null hypothesis should be rejected.
Fig 6.19
A 35-year-old Irish woman with polyhydramnios was delivered vaginally of a female

infant at 32 weeks' gestation. The antenatal ultrasound had shown a large abdominal
cyst. Intubation was performed electively on the neonatal unit. The AXR is shown.
What are the findings on the X-ray?
i. Oesophageal atresia
ii. Pulmonary hypoplasia
iii. Bowel perforation
iv. Hepatomegaly
v. Calcified abdominal mass
vi. Cardiomegaly
vii. Thoracic compression
255
v. Calcified abdominal mass
vii. Thoracic compression
b
C:
(I)
The X-ray shmvs a large abdominal calcified cyst with compression of the thoracic
� structures.
o·
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V\ Possible diagnoses include an ovarian cyst, choledochal cyst, mesenteric cyst, on1ental
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cyst, enteric duplication, meconium pseudocyst or cystic teratoma.
c..
It is in1portant here to exclude cystic fibrosis.
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� CF mutations, and cyst histology at laparotomy.
....
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-+,
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.... Outcome
,-+
::::; The lesion was a meconium pseudocyst, calcification of the cyst suggesting the diagnosis
(I)
z of a meconium. pseudocyst or a cystic teraton1a. Laparotomy identified a segment of

(I) adherent bowel containing a perforation with resultant inflammation, fibrosis and cal
� cification. The mucosal gland pattern was not consistent with cystic fibrosis. DNA
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there was no family history of CF. This antenatal diagnosis may be associated with
r-+ cystic fibrosis but can also occur in other diagnoses, e.g. volvulus or ileal atresia.
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256
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Fig 6.20
The 4-year-old daughter of a pharmacist was referred by her optician with reduced
visual acuity and bilateral red eyes. Between referral and review, she developed swell ing
of her left ankle and knee, and stiffness in her neck. On examination, the swollen joints
were all warm with mild limitation of movement but no fixed flexion deformity.
Remaining examination was unremarkable except for her eyes, which showed keratic
precipitates as a complication of anterior uveitis.
What is the most likely underlying diagnosis?
i. Rheumatoid arthritis
ii. Systemic lupus erythematosus
iii. Systemic sclerosis
iv. Reiter's disease
v. Still's disease
vi. Type I pauciarticular JIA
257
ANSWER TO CASE 6.20
vi. Type I pauciarticular JIA
Keratic precipitates are seen as fine white lines visible over the central cornea. They
consist of inflammatory cells from iris and uveal vessels which stick to the corneal
endothelium. Anterior uveitis is found in a number of infla1nmatory, auto-immune and
infectious diseases. It may be unilateral or bilateral. Early changes may be subtle and
QJ
detectable only by slit lamp examination. Management concentrates on determining a
::, systemic aetiology, preserving visual function, reducing ocular pain and eliminating
0..
inflammation. Anterior uveitis is seen in 15-30% of patients with pauciarticular JIA.
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Joint involvement may be mild or not evident at the tin1e of ophthalmic diagnosis.
The severity of the joint disease does not correlate with the risk of eye involvement.
(I)
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Vl For this reason, all children with a diagnosis of pauciarticular JIA need 3-monthly slit
- lamp examinations for at least the first 5 years of disease. Ninety per cent of patients
0
""'I have positive antinuclear antibodies. Neither rheumatoid factor nor HLAB27 is associ
r-+
::, ated. In type I pauciarticular JIA, joint disease normally occurs before the fourth
(I)
z birthday. Type I is 1nore common in girls who are at greater risk of chronic anterior
(I) uveitis (iridocyclitis). Type II primarily affects older boys who may subsequently
� develop spondyloarthropathy.
-n
0
3QJ Ophthahnological complications of anterior uveitis include posterior synechiae, acute
glaucon1a, cataracts, phthisis bulbi (degeneration of the globe) and pern1anent blindness.
r-+
m Posterior synechiae refers to adherence of the iris to the anterior lens capsule. Caught
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3 requires surgical management. Cataracts may form_ as a result of chronic inflanu11ation
or secondary to long-term topical or systemic steroid use. Phthisis bulbi is atrophy of
the globe; this is managed by enucleation for cosmetic reasons. Finally, in the absence
of globe degeneration, permanent blindness may result.
258
r
A 2-year-old boy with severe Hurler's syndrome is seen in outpatients. He has global
developmental delay and behavioural problems. He is thought to be a little pale, and s:
.,,
;:o
the blood results are as follows: (')
Hb 3.9 g/dl (')
MeV 54 fl
.,,
I
Wee 4.1 X 10x9/I n,
platelets 206 X 1 ox9;1 ;:::i.
N
i. G6PD deficiency
ii. Acute lymphoblastic leukaemia
iii. Fanconi anaemia
iv. Severe iron deficiency anaemia
v. Meckel's diverticulum
b. What treatment is required?
i. Irradiated packed cells
ii. Intravenous iron sucrose
iii. Oral iron supplementation
iv. Dietetic advice
v. Bone marrow transplant
vi. Blood transfusion
261
ANSWERS TO CASE 1.1
a. iv. Severe iron deficiency
b. iii. Oral iron supplementation
Hurler's syndrome is type I nrncopolysaccharidosis. Although normal at birth, dysmor
phic features develop after the first year of life. Developmental regression is usually
severe. In this patient, the developmental delay and behavioural problen1s meant that
he ate very poorly. His dietary intake of iron was virtually nil and anaemia developed
chronically.
As the patient is not cornpromised by the anaemia, in11nediate blood transfusion is
unnecessary, and n1ay even be dangerous. Iron supplementation ,vill have an effect in
2-3 days.
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262
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Fig 7.2
At 38 weeks' gestation a 25-year-old woman presented with reduced fetal movements

and therefore had a cardiotocograph performed.
a. Identify three main features (normal or abnormal) of the fetal heart rate on
the CTG?
i. Fetal tachycardia
ii. Normal baseline fetal heart rate
iii Hyperreactive trace
iv. Reactive trace
v. Type I decelerations
vi. Type II accelerations
vii. Normal beat-to-beat variation
b. In the presence of an abnormal trace, which of the following is not a risk
factor for the development of fetal hypoxia and acidosis?
i. Intrauterine growth restriction
ii. Infant of a diabetic mother
iii. Reversed end diastolic flow
iv. Intrauterine infection
v. Prematurity
vi. Post term
263
ANSWERS TO CASE 7 .2
a. ii. Normal baseline fetal heart rate
iv. Reactive trace
vii. Normal beat-to-beat variation
b. ii. Infant of a diabetic mother
The normal baseline fetal heart rate is between 110 and 150 bpm.
0, Norn1al baseline variability is betv,reen 10 and 25 bpm.
:::,
a.
This CTG is reactive: it shows normal variability around a norn1al baseline, with normal
)>
:::, accelerations of the fetal heart rate (due to fetal n10vements or uterine contractions).
-
V\
(I) There are no decelerations; the fetal heart rate does not fall belO\v 110 bpm throughout
"'"'I
V\ the trace.
Q Risk factors for hypoxia and acidosis include: intra-uterine growth restnct1on, intra
r-+
::::, uterine infection, prematurity, post term (>41 weeks' gestation), placental abruption,
(I)
and placental insufficiency.
z
(I)
� Different delivery units n1ay have slightly different guidelines but generally a paediatri
"Tl cian needs to be present for the following deliveries: prematurity (<36 weeks' gestation),
0
3
0,
small for gestational age, fetal distress (thick n1econium_ stained liquor, abnormal trace,
fetal scalp pH <7.20), multiple pregnancy, significant antepartun1 haemorrhage, fetal
r-+
m disease (congenital abnorniality, rhesus disease).
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264
A10-day-old boy was referred for endocrine evaluation due to persistent jaundice,
episodes of hypoglycaemia, difficulty with temperature regulation and small genitalia.
He was born at term by forceps delivery and required bag and mask resuscitation. His
s:
:::0
(")
Apgar scores were 3 at 1 min, 7 at 5 min and 8 at 10 min. He was admitted to the ,:,
{')
neonatal unit for i.v. glucose and settled before being transferred to the postnatal I
ward. Septic screen was negative. On examination, he was jaundiced, had no obvious ,:,
OJ
dysmorphic features and had a small penis with hypoplastic scrotum. Both testes were ;:.1.
felt in the scrotum. In view of his persistent symptoms, he had the following N
investigations:
Blood group A+ve
Mother's blood group A +ve
Direct Coomb's test negative
TSH 1.7 mU/I (normal range 0.5-6 mU/I) v
Thyroxine 57 nmol/I (normal range 90-220 nmol/I) �
Cortisol 41.3 nmol/I (normal range 180-700 nmol/l)J;,
The result of a glucagon stimulation test was as follows:
Table 7.3.1
Time (min) -15 0 30 60 90 120 150 180
Glucose (mmol/1) 3.9 3.7 4.0 4.3 4.0 3.3 4.7 3.0
GH(mU/1) 3.7 3.8 3.8 6.0 9.7 9.4 6.9 6.9
Cortisol (nmol/1) <70 <70 <70 <70
Glucose was administered i.v. at 120 min, as the bedside BM was 1.6 mmol/1.
Other baseline endocrine tests showed:
FSH <1 IU/I
LH <0.3 IU/I
Testosterone 1.9 nmol/I
ACTH <10 ng/I
The urinary steroid profile showed that steroid levels were fairly low suggestive of some
degree of hypoadrenal hypofunction.
i. Hyperinsulinism
ii. Congenital adrenal hyperplasia
iii. Congenital hypothyroidism
iv. Congenital hypopituitarism
v. Congenital adrenal hypoplasia
vi. Conn's syndrome
265
ANSWER TO CASE 7 .3
iv. Congenital hypopituitarism
Congenital hypopituitarism (CH) is the likely diagnosis. Mutations in the pituitary
developmental transcription factor genes (POUlFl, PROPl or HESXl) account for
the majority of cases of CH. Dynamic pituitary testing shows a very inadequate cortisol
and GH response in a neonate. The con1bination of GH and ACTH deficiencies in
O.J
the newborn may result in severe hypoglycaemia that responds only to horn10ne
::) replacement. Prolonged jaundice in a neonate should prompt the measurement of
0..
thyroid function. Thyroid function shows low levels of T4 with norm.al TSH, confirm
)>
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ing pituitary hypothyroidism.. The combination of small penis and hypoplastic scrotum
� suggests hypogonadotrophic hypogonadisrn. but LH and FSH levels are difficult to
�
V,
interpret in the immediate neonatal period.
-+,
0
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An MRI of the hypothalamic pituitary area is needed to help confirm the diagnosis.
r-+ In approximately half of all patients with CH, there is attenuation or interruption of
=r
(1) the pituitary stalk with or without associated corpus callosum defects. Risk of intellec
z
(I)
tual disability is higher if the patient has a defect in corpus callosum. In this case, there
was a hold-up of the neurosecretory granules at the level of the hypothalam.us. Oph
.,,
0
thalmological assessment should be performed to look for optic nerve atrophy. Meas
3
O.J
urement of gonadotrophins at about 3 m.onths may help to confirm hypogonadotrophic
hypogonadisrn as there is a natural surge in the hormones in the first few n1.onths of
r-+
m life.
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Management involves the instigation of a replacement dose of hydrocortisone (8-
3 10 mg/n}) and thyroxine (100 mcg/m2). In this case, resolution of hypoglycaemia
occurred, but sometimes GH replacement in addition may be necessary at this early
stage. The parents need to be given appropriate information as to the dose adjustment
of hydrocortisone during intercurrent illnesses (i.e. doubling of dose of hydrocortisone)
and taught how to use i.m. hydrocortisone in case of emergency. Assuming the
hypoglycaemia resolves with hydrocortisone, consideration for GH replacement can be
deferred initially. Puberty will need to be induced at 12 years (assuming no spontaneous
puberty) with testosterone.
266
A 9-year-old girl presented with a large swelling in her neck which had been increasing
in size for 2 weeks. She had been feeling unwell with a slight temperature. On
examination there was a 4 cm x 3 cm swelling anterior to the left sternomastoid which
was erythematous and mildly tender; it became fluctuant over the next few days.
Serology to Bartone/la hense!ae was positive.
-0
Investigations showed: OJ
;::i.
Hb 12.6 g/dl
wee 8.6 x 109/I
N

CRP 12 mg/I
i. Atypical mycobacterial infection
ii. Cat-scratch disease
iii. Lyme disease
iv. Lymphogranuloma venereum
v. Wegener's granulomatosis
b. What complications of this disease may occur?
SELECT TWO POSSIBLE ANSWERS
i. Cardiomyopathy
ii. Myelitis
iii. Encephalopathy
iv. Glomerulonephritis
v. Thrombocytosis
vi. Peripheral neuropathy
267
ANSWERS
a. ii. Cat-scratch disease
b. ii. Myelitis
0 iii. Encephalopathy
C:
(I)
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It is important to elicit whether there is a history suggesting recent infection in the
head or neck, e.g. sore throat, scalp infection, etc.; if there has been any contact with
Vl
OJ tuberculosis or unpasteurised milk? Any contact with cats? Or any foreign travel?
:J
a.. Investigations should include: FBC and film; viral serology, including EBV and CMV,
)> and serology to Bartone/la henselae, which causes cat-scratch disease; CXR and Mantoux,
:J
Vl to help differentiate from TB; and biopsy of the swelling n1ay be considered.
�
(D
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In 75% of cases of cat-scratch disease, a lesion appears at the site of inoculation between
-+, 3 and 10 days after the scratch. The commonest site of lymphadenopathy is the
0
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..+
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(D In uncomplicated cases, no treatment is required. Typically the swelling slowly resolves,
z
(D
unless there is an underlying imnmnodeficiency. If treatment 1s needed, rifan1picin,
� cotrimoxazole, ciprofloxacin or gentamicin can be used.
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0 Numerous con1_plications have been reported, the most conunon being neurological,
3 including encephalopathy, cranial and peripheral nerve lesions and rn.yelitis. Hepatitis,
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..+ osteomyelitis and thrombocytopenia purpura can also occur.
m
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3
268
A 6-week-old breast-fed baby boy is referred to a paediatrician because he is failing to
thrive. He was born at term with a birth weight of 3900 g and no perinatal problems.
Since 2 weeks of age, he has been described as chesty and this was felt to be due to
an upper respiratory tract infection, as his older brother was suffering from one at the
time. Four weeks later and after a course of antibiotics, he is no better and is now
appearing pale and sweaty when feeding.
On examination, he appears thin, his weight being on the 10 th centile. There are no
signs of intercurrent viral illness. Although not overly distressed, he is tachypnoeic and
has intercostal recession. His oxygen saturation is 82% in air. He is tachycardic. His
pulses are rather weak. There is a right parasternal heave and a systolic murmur heard
at the pulmonary area with a widely split second sound and a loud P2. ECG indicates
right atrial and ventricular enlargement. CXR shows a large heart, increased pulmonary
vascularity and a large square shaped supracardiac shadow.
a. What is the likely diagnosis?
i. Patent ductus arteriosus
ii. Truncus arteriosus
iii. Total anomalous pulmonary venous drainage
iv. Transposition of the great vessels
v. Large VSD
b. What treatment is initially indicated?
i. lndomethacin
ii. Diuretics
iii. Prostaglandin infusion
iv. Urgent cardiac surgical opinion
v. ACE inhibitors
269
ANSWERS TO CASE 1.5
a. iii. Total anomalous pulmonary venous drainage
b. iv. Urgent cardiac surgical opinion
The diagnosis is unobstructed total anomalous pulmonary venous drainage. In this
infant, the pulmonary veins formed a confluence which drained into the superior vena
cava causing total comm.on mixing and marked volume overloading of the right heart.
OJ
The child was therefore 1nildly cyanosed and breathless. In this infant, blood was able
::J to reach the left side of the heart through a large ASD. In some children with an intact
0..
atrial septum or restrictive ASD, there may be a significant hypoplasia of the left side
)>
::J
VI
of the heart. There are three types of total anomalous pulmonary venous drainage -
supracardiac, as in this case, cardiac or infracardiac. The lesion can also be obstructed
�
(1)
VI or non-obstructed. Obstructed cases tend to present with severe respiratory distress and
-h cyanosis in the neonatal period, the severe pulmonary venous congestion on X-ray
0
� often leading to a misdiagnosis as respiratory disease. If pulmonary venous return is
,-+
:::; obstructed, however, the radiological clue is n1arked pulmonary venous congestion and
(1)
hepatomegaly with a small heart shadmv.
z
(1)
� The condition is a paediatric cardiac surgical emergency and therefore the child should
"Tl have an urgent echocardiogram and be transferred to a paediatric cardiac unit as soon
0
3
OJ
as possible. For those children who survive to surgery, there is around a 10% early
mortality. Thereafter the prognosis is best for those children who do not have puln10-
,-+
m nary arterial hypertension.
><
OJ
270
A 20-month-old boy was seen in a community paediatric clinic because of concern that
he was not yet walking. His mother informed the paediatrician that all other aspects of
his development were normal but he was showing no signs of starting to walk. On
questioning, the doctor was informed that the child had been a normal delivery at 36
weeks' gestation weighing 2800 g, and had needed no neonatal intervention. He had a
normal 4-year-old brother who had walked at 16 months and there was no other
family history of note. His weight was progressing along the 25 th centile and height
along the 9th centile.
What is the most likely diagnosis in this case?
i. Global developmental delay with late walking
ii. Mild cerebral palsy
iii. Becker muscular dystrophy
iv. Duchenne muscular dystrophy
v. Normal variant
vi. Myasthenia gravis
271
ANSWER TO CASE 7.6
v. Normal variant
D A detailed assessn1ent of all aspects of development is needed:
C
speech - he should have approxin1ately 5 vwrds and may be using simple
�
<D
combinations
o·
:::i social - nunages a cup/den1ands objects by pointing
V\
0)
fine motor - scribbles/turns 2-3 book pages at a time/builds tavver of three
::J blocks
a..
gross motor - pulling to stand/cruising
)>
:::i
V\ Are there any specific features such as crawling or botton1 shuffiing or dernonstration
of a Gower's n1anoeuvre?
.....
Vl
-+, A thorough physical examination including neurodevelopmental assessment 1s
0
..... required.
,-+
:::J"
ro The diagnoses to be considered fall into two main groups:
z
ro
1. Normal variant late vvalkers:
These will develop normally. Indications of this are rolling, creeping or bottom_
,,
0
shuffling. Other features may be reduced tone especially of the lower limbs, late
3
OJ
sitting, lax joints and a family history of late walking. Ninety-seven per cent of
children walk by 18 months of age (6 steps unaided).
,-+
m 2. Newly diagnosed conditions which may present with late walking:
>< a. Duchenne nrnscular dystrophy - affects 1 : 3500 rnales and is diagnosed by ele
OJ
3 vated CPK and muscle biopsy

b. Cerebral palsy - mild or moderate spastic diplegia may present as late walking
c. Learning difficulties - late walking may be the first sign of global delay
This child was a normal variant late walker who started to walk 2 weeks later.
272.
Fig 7.7
A preterm infant was born at 25 weeks' gestation. The cranial ultrasound scan taken
on day 1 of life was normal. On day 2, the infant suffered a profound collapse and
required resuscitation. Figure 7.7 shows a T2-weighted MRI brain scan taken at
13 weeks' postnatal age.
i. Hydrancephaly
ii. Bilateral subdural haemorrhages
iii. Parenchymal leukomalacia
iv. Post-haemorrhagic ventricular dilatation
v. Cerebral atrophy
273
TO CASE 7.7
iv. Post-haemorrhagic ventricular dilatation
Acute clinical consequences of a large intraventricular haemorrhage include acidaemia,
hypotension, seizures, anaemia and impaired consciousness.
The infant's head circumference increased by two centile lines between 38 and 40
weeks corrected gestational age. He was irritable, feeding poorly and vomiting occa
OJ sionally. A ventricular tap was performed.
a.
::,
The next step in management would be to refer the baby for a neurosurgical opinion.
)>
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VI
The infant may require a ventricular reservoir device to enable frequent CSF aspiratio n
to be carried out more safely. The infant may ultimately require a ventricular shunt.
(I)
'""'I
VI
-h Procedure: ventricular tap
0
'""'I
,-+ The surface landmark used for the ventricular tap is the lateral margin of the anterior
::J"
(I) fontanelle, not medial to the pupillary line. A medial passage could result in aspiration
z
(I)
of the dural sinus. The needle should be directed forwards and slightly inwards tovvards
� the inner canthus of the opposite eye. Insertion should not exceed 4-5 cm and will
"T1 often aspirate CSF at a shallow depth of 1 cm in infants with post-haemorrhagic ven
0
3
OJ
tricular dilatation.
,-+
m
><
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3
274
A 22-month-old girl presented with a 7-day history of upper respiratory symptoms and
2 days of swollen legs. She was not eating well and occasionally complained of
abdominal pains but remained active. She was a full-term normal delivery with no past
medical history of note. She was not on any medication and the rest of the family was
well. On examination she was well but had markedly oedematous legs. Her blood
pressure was 125/85 and pulse 120/min. She had a distended abdomen with shifting
dullness. Investigations: Hb 13.4 g/dl, wee 15.0 x 109/I, platelets 676 x 109/1, Na
138 mmol/I, K 4.3 mmol/I, urea 4.5 mmol/I, and creatinine 32 µmol/1.
a. What two other investigations would you request?
i. Abdominal ultrasound
ii. Pulse oximetry
iii. Urinalysis
iv. Blood protein
v. Serum osmolality
vi. Four-limb blood pressure
b. What other blood result is likely to be abnormally high in this condition?
i. lgA
ii. Coagulation inhibitors
iii. (3
iv. Lipids
c. What would your management be?
i. Fluid restriction
ii. High protein diet
iii. Steroids
iv. i.v. albumin infusion
v. i.v. immunoglobulin
275
ANSWERS TO CASE
a. iii. Urinalysis
iv. Blood protein
,0
C b. iv. Lipids
(I) i. Fluid restriction
� C.
o· iii. Steroids
:J
VI
OJ
This child has nephrotic syndrome. Nephrotic syndrome is characterised by massive
:J urinary protein loss leading to hypoproteinaemia and oedema. The cause of the protein
Cl.
loss is unknown but capillary membrane pern1eability is increased. This increased fil
)>
:J tered load overcomes the tubular reabsorption capacity, hence proteinuria. The plasma
oncotic pressure falls and causes oedema. With progression of the disease the intravas
(I)
VI cular volume becomes depleted and the renin-angiotensin system is stimulated. This
-1-, may lead to hypertension.
,-+ The liver increases protein synthesis in order to try to maintain adequate plasn1a
:::r
(1) albun1in levels. As a consequence, plasma lipoprotein levels increase. However, lower
z
(I)
levels of plasma lipoprotein lipase are also present and both factors lead to raised plasma
cholesterol and lipids.
,,
0 Of all childhood nephrotic syndrome, 90% is idiopathic; of these, 85% is minin1al
3
OJ
change nephrosis on histopathology; 5% have mesangio-proliferative type and 10% focal
,-+ glomerular sclerosis; the remainder is congenital or associated with glomerulonephritis,
m tmnours or drugs.
><
CJ
3 The n1ost frequent com_plication of nephrotic syndrome is infection. There are n1any
theories for why this is so, such as loss of inrnrnnoglobulins and complement proteins
in the urine. Streptococcus pneunwniae is the most common pathogen and penicillin
prophylaxis is therefore recommended. There is also an increased incidence of throm
bosis, both venous and arterial.
Treatment consists of fluid if there is any evidence of intravascular volun1e depletion,
then fluid restriction, accurate fluid intake and output measurements, daily weights,
and continuing urinalysis and steroids. Most cases are responsive to steroid therapy. If
there is no response after one month, renal biopsy is indicated. Relapses are treated in
the same way as the initial episode. Frequent relapsers may need a long course of
steroids or other drugs, e.g. cyclophospham.ide, to put them into remission. In most
children, steroid responsive nephritic syndron1e will have resolved by the end of the
second decade.
276
Fig 7.9
A 5-month-old boy was referred by his GP to paediatric outpatients because his weight
was "escalating off the top of his growth chart with no signs of reaching a plateau".
His development was normal. His growth chart is shown.
a. Which pieces of information would help you make a diagnosis?
i. Neonatal history of overfeeding
ii. Maternal drug history in pregnancy
iii. History of floppiness
iv. History of hypoglycaemia
v. Sleeping pattern
vi. History of diarrhoea
vii. Head circumference
b. Which of the following diagnoses would be most likely?
i. Laurence-Moon-Biedl syndrome
ii. Overfeeding
iii. Prader-Willi syndrome
iv. Congenital hypothyroidism
v. Zellweger syndrome
vi. Rubenstein-Taybi
vii. Diabetes mellitus
2Tl
a. iii. History of floppiness
iv. History of hypoglycaemia
vii. Head circumference
b. ii. Overfeeding
In the first year of life, growth is almost entirely nutrition-dependent. By the age of
2 years, GH receptors are present, and hormonal causes become significant.
It is important to elicit a thorough dietary history of any child referred for growth
concerns. This includes what the feeds consist of, how formula feeds are made up, and
how much and how often feeds are given. A developmental history would help dis-:
tinguish certain syndromes such as Soto's and Prader-Willi. Children with Prader-Willi
are characteristically small and hypotonic at birth, with a history of poor feeding. The
size of other family members and the child's head circumference should also be
r+ measured.
::r
(I)
Rare causes that should be considered:
z
(I) Soto's syndrome (cerebral gigantism) - characteristics include a large child, con,
� monly with developmental delay.
"TI
0 Beckwith-Wiedemann - characteristics include obesity, hyperinsulinaemic hypogly
3 caemia, macroglossia, exomphalos, visceromegaly, and parallel creases on the ear
OJ
r+ lobes.
m Prader-Willi - characteristics include obesity, developmental delay, hypotonia, short
X
OJ
stature, hypogonadism and diabetes mellitus. These children are characteristically
3 small at birth, with a history of poor feeding; typically, obesity occurs after the
first year.
Laurence-Moon-Biedl - characteristics include short stature, hypogonadism, diabe
tes insipidus, polydactyly and retinitis pigmentosa. Obesity characteristically
occurs after the first year.
278
A 15-week-old infant was admitted to the paediatric ward with a history of possible
choking. Her mother reported that she had noted a mild cough at lunchtime that had �
:::0
settled quickly and she had thought no more about it. However, that evening whilst in
the bath the infant had begun coughing again, this time more violently. Despite there n
being no apparent history of foreign body aspiration her mother still described the :::c
-0
episode as a choking type cough. The baby had not fed for 4 hours previously. The GP OJ
was called and felt the air entry to be markedly different on each side and queried a ;:+
N
pneumothorax. The baby had previously been well.
On arrival she was pink and well perfused. She fed well and was happy and smiling.
Oxygen saturations were 96% in room air. She was afebrile with some peri-nasal
crusting and had mild to moderate sternal recession. Air entry was decreased over the
left lung. However, on review by the registrar, when she was asleep, there was minimal
respiratory distress and air entry was said to be normal. A diagnosis of upper respiratory
tract infection was felt to be more likely.
The following morning she was reviewed. Again she had moderate sternal recession
and markedly decreased air entry over the left lung.
i. Bronchiolitis
ii Foreign body
iii. Mural or extra-mural obstruction of the left main bronchus
iv. Gastro-oesophageal reflux with aspiration
v. Cystic fibrosis
b, Choose the most appropriate initial investigations?
i. Bronchoscopy
ii. CXR
iii. Sweat test
iv. Upper GI contrast
v. pH study
279
ANSWERS TO 7.10
a. ii. Foreign body
iii. Mural or extra-mural obstruction of the left main bronchus
,0 b. i. Bronchoscopy
C
(D
!!I. ii. CXR
o·
:::::l A CXR was performed ,vhich, although rotated, suggested hyperluceny of the left
V'I
OJ
lung. A CT scan of her chest suggested the diagnosis of bronchogenic cyst that was
:::::l partially obstructing the left main bronchus. This was confirmed at thoracotomy where
a..
it was successfr1lly removed. She subsequently made a good post-operative recovery.
)>
:::::l
�
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(D
V'I
-
0
""'
r+
::;
ro
z
ro
�
-,,
0
3
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r+
m
X
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280
A 2-day-old infant was admitted to the neonatal unit because a bluish discolouration
was noted periorally, on the forehead and on both hands. Six hours later, his oxygen �
requirement gradually increased and he required 60% oxygen to maintain saturations ;::o
("'\
around 93%. The following investigations were performed: CXR showed a normal "'ti
("'\
cardiac shadow and clear lung fields; ECG was within normal limits; four-limb blood I
pressures were within normal limits; echocardiogram was normal; hyperoxia test was "'ti
OJ
normal; and arterial blood gas in 40% oxygen was - pH 7.31, pCO26.1
---- kPa, pO2 ;:'.l.
18.12 kPa, BE -4.1. N

i. Persistent pulmonary hypertension of the newborn
ii. Group B Strep septicaemia
iii. Methaemoglobinaemia
iv. Cyanotic congenital heart disease
v. Hyaline membrane disease
281
ANSWER TO CASE 7 .11
iii. Methaemoglobinaemia
This infant has methaemoglobinaemia. A methaemoglobin level should be checked
(normal <1 %). A detailed family history and maternal drug history including the anaes
thetic drugs given during delivery must be sought.
In normality, the oxidation of the iron moiety of haen10globin from the ferrous to the
ferric state results in the formation of n1ethaemoglobin. Methaemoglobinae1nia occurs
when ferric haemoglobin cannot be converted back to ferrous haemoglobin by the
normal reducing n1echanisms. High concentrations of methaemoglobin lead to a
reduced o::-...7gen carrying capacity due to the red cells delivering less oxygen, and a left
shift of the haemoglobin dissociation curve. Therefore, there is a reduction in the o::-...7gen
carrying capacity of the red blood cell.
Methaemoglobinae1nia may be congenital or acquired. The congenital forn1 may be a
familial autosomal recessive NADPH-cytochrome 65 reductase (diaphorase 1) defi
ciency or an autosomal don1inant haemoglobin M disease. A number of substances are
capable of oxidising haen10globin directly and will do so in vitro; these include nitrites,
nitrates, chlorates and quinines. The diagnosis in this case is autosomal recessive con
"TI
0 genital methaen1oglobinaemia.
3
OJ
r+
m
><
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3
282
A 2-year-old Caucasian girl, unwell with a 24 h history of fever and vomiting was
referred by her GP who noted that she had a maculo-papular "flea-bitten" rash on her s;:
:::0
trunk. Her mother reports that the child had become worse in the last hour, the rash ("')
iJ
had spread to her limbs, and she now appeared confused. On examination she was ("')
tachycardic (pulse 140 bpm) with a capillary refill time of 4 s and had no meningism. I
iJ
Some of the maculo-papular lesions were now 3-4 mm large and non-blanching. OJ
;:l.
Which diagnosis should be considered as a matter of priority? N

i. Rocky Mountain Spotted fever
ii. Acute lymphoblastic leukaemia
iii. Meningococcal septicaemia
iv. Bleeding diathesis
v. Henoch-Schonlein Purpura
vi. Lyme disease
vii. Necrotizing fasciitis
283
ANSWER TO 7.12
iii. Meningococcal septicaemia
,0 Meningococcal septicaen1ia is the most important diagnosis to consider, and a maculo
C:
(I)
papular "flea-bitten" rash may precede the typical purpuric rash in many children. This
(/)
fulminant presentation is typical of meningococcaemia, but haemorrhagic rashes n1ay
o·
r+
::}
also be caused by Henoch-Schonlein Purpura (HSP), acute lymphoblastic leukaemia,
(/)
Q)
bleeding diatheses, and in travellers returning from_ North America, Rocky Mountain
::} spotted fever.
0..
)> The immediate n1anagement is critical in reducing n1ortality, and early consideration
::}
(/) of the diagnosis is important. Management should be proactive, anticipating problems
CD rather than responding to them. Elicit senior clinical support, with sufficient hands to
"""I
V, stabilise and manage the child rapidly. Establish venous access (at two sites), and give
-+,
0
"""I
a fluid bolus of 20 mg/kg normal saline or colloid, and an i.v. beta lactam antibiotic
r+ (e.g. cefotaxin1e/ceftriaxone). Assess the response and repeat if necessary. Consider an
:::,
CD inotrope infusion, and if more than 40 ml/kg of fluid has been required to stabilise, it
z is advisable to intubate and ventilate early. Local policy will determine whether one
CD
transfers the child when stable to PICU or to a regional referral unit.
"Tl
0 Blood should be taken for FBC and differential count, clotting studies, U&E, and,
3OJ depending on severity, blood gases. Pulse, respiratory rate, blood pressure and core and
r-+ peripheral te1nperatures should be rnonitored. Blood cultures are usually positive in
m children ,vho have not received prior antibiotics, and Gram_ staining of an impression
><
OJ slide from a skin scraping of a purpuric lesion can give an irmnediate result, even fol
3 lowing antibiotics. PCR results are now available in less than a week in the UK (use
an EDTA tube). Serology rnay be helpful, but requires both acute and convalescent
samples.
The GP should give parenteral penicillin prior to referral, if diagnosis is considered.
Public Health usually arranges antibiotic chemo-prophylaxis for close contacts, usually
rifampicin 10 mg/kg (maximum 600 mg) b.d. for 2 days. Alternatives are a single i.1n.
dose of ceftriaxone, or oral ciprofloxacin. Public Health will also be aware of possible
clusters of disease, which may require wider antibiotic chemoprophylaxis, and for group
C disease - immunization. They can also alert the community to recognise and report
symptoms and signs early.
Meningococcal C conjugate vaccine is now given in the routine immunisation schedule
in the UK, and has dramatically reduced the prevalence of disease. There is also a
polysaccharide vaccine for groups A, C, W135 and Y, but not for the commonest UK
group B. Antibiotic chemo-prophylaxis, given early to close contacts reduces secondary
cases.
284
s;:
;::o
("'\
'"t1
("'\
:c
'"t1
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�
N
Fig 7.13
A 6-year-old boy with no past medical history of note has this chest radiograph during
the recovery phase after a recent severe pneumonic illness.
What are these appearances likely to be due to?
i. Pneumocystis carinii
ii. Right-sided diaphragmatic hernia
iii. Congenital cystic adenomatoid malformation of the lung
iv. Pneumatocoeles
v. Clostridial infection
vi. Hydatid disease
285
ANSWER TO CASE 7 .13
iv. Pneumatocoeles
D The chest X-ray demonstrates that the patient is intubated with the tip of the endotra
C cheal tube in a satisfactory position. A right internal jugular venous line is also present
m.
o·
::,
with the tip probably in the superior vena cava. Cardiac n1011itoring leads are also
noted, as is the presence of a nasogastric tube and chest drain. These lines and tubes
VI
0,
indicate that the pneumonia was quite severe. Within the lungs are bilateral nrnltiple
::, ring shadO\,vs which are relatively symmetrical, measuring up to 4-5 cm in diameter.
a..
The thickness of their walls is quite regular and thin. Air-fluid levels are not seen
)>
::, within them_. All areas of the lungs are affected. There is probably a small residual
�
(I)
pneumothorax at the right costophrenic angle and right-sided subcutaneous surgical
--;
VI
emphysema.
--1-,
0
--;
The most likely cause of multiple cystic air collections in the lungs following pneu
,-+ n10nia is the developn1ent of pneun1atocoeles. These are interstitial accunrnlations of
::;
(I) air probably due to obstructive over-inflation. They are characteristically seen follO\ving
z
(I)
bacterial pneumonia, particularly due to Staphylococcus aureus (the diagnosis in this
� case), but also from other bacteria, including H. influenzae, streptococcus, klebsiella,
.,,
0
E. coli, and M. tuberculosis. They may rapidly enlarge and cause mediastinal displace
3
OJ
ment and even perforate into the pleural space causing a pyopneumothorax. In a patient
with pneumonia, they can, on occasion, be difficult to differentiate frmn a lung abscess,
,-+
m and in fact there is no foolproof method for radiologically rnaking such a differentia
>< tion, particularly if inflanm1-atory exudate from a surrounding infected area seeps into
OJ
3 them and gives rise to an air-fluid level. Pneumatocoeles are more commonly multiple
than lung abscesses and more often have a thin smooth wall. In addition, clinical dif
ferentiation should be possible since pneumatocoeles usually develop during the healing
phase (10-14 days into the course of the infection) while the patient is clinically
improving whereas a lung abscess develops early on, while the patient is still quite ill.
Other causes of similar pneumatocoeles include hydrocarbon aspiration, Langerhans cell
histiocytosis and lung trauma, including barotrauma.
The natural history of pneumatocoeles is one of spontaneous resolution. Even large
pneumatocoeles can resolve in a few days, especially if it is of infective aetiology..
Occasionally small thin-walled cysts can be observed for several months following the
initial insult; most resolve without sequelae.
286
A 15-year-old girl develops a diarrhoeal illness with pyrexia. As the diarrhoea is
resolving she is noted to be jaundiced. She has pale stools and dark urine. She has a
5 cm liver palpable and a spleen tip. Her liver function tests are as follows:
s:
:::0
ri
Bilirubin 198 µmol/I ""O
ALT 1085 U/I ri
:::c
AST 995 U/I ""O
OJ
GGT 60 U/I """I
r+
ALP 785 U/I N
Albumin 40 g/I
What further tests would you perform to help make the diagnosis?
i. Viral serology
ii Stool for virology
iii. Abdominal ultrasound scan
iv. Liver biopsy
v. Blood gas
vi. HIDA scan
vii. Toxicology screen
viii. Ammonia
287
ANSWERS TO CASIE 7 .14
i. Viral serology
ii. Stool for virology
vii. Toxicology screen
The most likely diagnosis is a viral hepatitis, especially hepatitis A. The other hepatitis
viruses, especially B, are also possibilities if she has risk factors. There are many other
a,
viruses which also cause acute hepatitis, the most common being EBV, echovirus,
::J coxsackie virus, parvovirus and adenovirus.
0..
)> In a girl of this age, the possibility of drug toxicity should be considered particularly
::J
VI paracetan1ol and recreational drugs (ecstasy, solvents, cocaine, etc.).
�
ro
�
VI Factors from the history that should be specifically enquired about include: any history
- of foreign travel, blood transfusions, i.v. drug abuse, sexual contact, contacts with viral
0
� illnesses, overdoses or recreational drugs.
,+
:::,
ro Viral serology and stool for viruses should be sent to help make the diagnosis, as well
z as a toxicology screen should there be any concerns from the history.
ro
� Exan1ination for encephalopathy and measurement of prothrombin tin1e would help
"Tl
0 ascertain whether she were developing acute liver failure and would need inm1ediate
3a, referral to a liver centre. If either of these were abnormal or if there was ongoing
,+ concern, the folhwing should be checked: acid-base status, glucose, ammonia, and
m lactate.
><
CJ
3 Hepatitis A accounts for 20-25% of acute hepatitis. The picture is typically of hepatitis
with some obstructive features. The major complication is acute liver failure which
occurs in approximately 0.1 %1 of infected children. Warning signs of progressive disease
are grossly elevated transaminases; increased prothrombin time; rapidly increasing
bilirubin; decreasing liver size and increasing lethargy/ confusion. Once liver failure
develops then acid-base derangements, renal compromise, hypoglycaemia and increas
ing plasma ammonia occur.
Acute abdominal pain may develop, most likely due to acute pancreatitis in both the
acute and convalescent phase of hepatitis A, but this could also be due to acute hepatic
enlargement or a surgical cause. Investigations would include an ultrasound of liver,
biliary tree and pancreas, serum amylase, and possibly a surgical assessment.
288
A 10-year-old Caucasian girl was found to have proteinuria. She had a 4-year history of
rheumatoid factor positive polyarticular juvenile idiopathic arthritis (JIA) that had been �
::::0
treated with weekly i.m. methotrexate over the preceding 3 years. The dose of n
methotrexate had recently been reduced from 20 mg to 10 mg because of raised "'O
n
hepatic transaminases. Her arthritis is not currently well controlled. There was no history ::r:
of pre-existing renal disease and no family history of renal problems. Her grandmother "'O
OJ
had sarcoidosis. On examination, she was normotensive. There was no peripheral ;:l.
oedema. She had evidence of active arthritis in both knees. Remaining examination was N
unremarkable. Urinalysis showed moderate proteinuria with a protein : creatinine ratio

of 200 (normal range <12.5). Serum albumin was in the normal range. There was no
biochemical evidence of renal impairment.
Which of the following are not possible causes of the proteinuria?
1. Nephrotic syndrome
ii. Methotrexate nephropathy
iii. Sarcoidosis
iv. Renal amyloidosis
v. Interstitial nephritis
289
i. Nephrotic syndrome
v. Interstitial nephritis
.0
C
ro Polyarticular JIA affects more than four joints in the first 6 months. Rheumatoid factor
V\
o· positive disease typically has a worse prognosis and often requires early treatment with
,-+
:::s methotrexate. An1yloid proteins can accumulate in any chronic inflarnn1atory condition
V\
Q,J
and may affect up to 10% of children with JIA. Renal an1yloidosis may cause isolated
:::s proteinuria. There is a family histo1y of sarcoidosis and, although isolated renal involve
a..
ment is rare, renal sarcoidosis should be considered. Methotrexate has many adverse
)>
:::s effects including nephropathy. Proteinuria seconda1y to methotrexate toxicity must
�
ro
therefore be included in the differential diagnosis. Routine n1011itoring of patients on
methotrexate includes periodic full blood count, hepatic and renal biochen1istry, uri
-+, nalysis and chest radiograph. The clinical picture is not one of nephrotic syndrome.
0
., Interstitial nephritis is unlikely in the absence of haen1aturia.
,-+
::,
ro Proteinuria is a cardinal sign of glomerular disease and, at this level, warrants investiga
z
ro
tion into the underlying cause. Basic investigation includes renal biochemist1y, quantita
� tive urinalysis and a renal tract ultrasound. Results of these along with the clinical
.,,
0
histo1y guides further investigation. In this case, the n10st obvious next investigation is
3
OJ
an estin1ation of serum arnyloid protein. An1yloidosis is ,veil recognised in JIA and an
important diagnosis to make early. A renal biopsy would differentiate betvveen an1y
r+
m
loidosis and methotrexate-induced nephropathy, or suggest an alternative diagnosis. In
>< this case, the serun1 amyloid A protein was raised at 102 mg/1 (normal range <10).
OJ
3 Congo red staining of a renal biopsy specin1en confirmed glomerular deposition of
an1yloid protein. An1yloidosis seconda1y to JIA is classically treated with chloran1bucil
which may reverse proteinuria and prolong life. In addressing the problem of proteinu
ria, it is important not to ignore the underlying disease, and with previous hepatic
complications of higher dose methotrexate, the options are liinited. The TNF-a
antagonist Etanercept has recently becorne available and is being increasingly used as
an adjunct to other therapies in the management of JIA.
290
A female baby was admitted to the paediatric ward at the age of 4 days with a history
of vomiting, poor feeding, lethargy and jaundice. She had been born at term to a 29- s::
year-old primigravida, and had had a birth weight of 3120 g. The baby's mother had n
-0
been well during pregnancy; in the past, she had suffered two generalised seizures but n
was not taking any medication. The parents were unrelated. There was no family :c
-0
history of jaundice or liver disorder, nor was there any history of sudden neonatal OJ
death. The birth had been uncomplicated, and the baby was being breast fed. On �
N
examination, she was dehydrated, having lost 13% of her birth weight, and obviously
jaundiced. Systemic examination was otherwise unremarkable.
The following tests were carried out:
Total bilirubin 387 µmol/I (conjugated 6)
FBC normal
Blood sugar normal
Direct Coombs' test (DCT) negative
Mother's blood group O positive
Baby's blood group O positive
Urine microscopy normal
Following an initial reduction in the bilirubin level after phototherapy and i.v. fluids, the
level rose again and 4 days later was 362 µmol/I (conjugated 79). The baby was well
hydrated but had now developed a 3.0 cm hepatomegaly. The stools were pigmented,
and eye examination revealed normal bilateral red reflexes. Further phototherapy was
given and, as there was a suspicion of a possible metabolic disorder, breast feeds were
stopped and a particular formula feed was introduced. This resulted in a dramatic
improvement in the infant's condition and a resolution of the jaundice.
i. cx-1 antitrypsin deficiency
ii. Galactosaemia
v. Niemann-Pick disease
291
ii. Galactosaemia
The diagnostic clue was that whenever breast feeds ,vere stopped, the baby's condition
improved clinically. Classical-form galactosaemia is caused by an inherited deficiency
of the enzyme galactose-1-phosphate uridyl transferase (GAL-1-PUT). Further inves
tigations include: LFTs, clotting studies, blood cultures, urine reducing substances,
ru thyroid function tests, glucose-6-phosphate dehydrogenase status, galactase-1-phosphate
::::l uridyl transferase activity (Beutler test), urine/blood amino acids and urine organic
a..
acids. There is a high risk of E. coli septicaemia.
)>
:::::i
Galactosaemia is an inherited autosomal recessive disorder (1 in 45 000 live-births),
most patients being homozygous or heterozygous for Q188R nrntation. Deficiency of
"""I
I/)
galactose-1-phosphate uridyl transferase causes accumulation of galactose-1-phosphate
-+,
0
"""I
in the liver, brain, lenses, kidneys and adrenal glands. If fed lactose (a disaccharide of
,-+ glucose and galactose), infants present with vomiting, diarrhoea, failure to thrive,
::::r
(I) developmental delay or retardation, cataracts, jaundice or cirrhosis. Examination may
z also reveal hepaton1egaly, a full fontanelle, bleeding or excessive bruising and evidence
(I)
of encephalopathy. Biochen1ical findings are abnorn1al LFTs, unconjugated or com
.,,
0
bined hyperbilirubinae1nia, abnormal clotting, raised plasma amino acid levels (pheny
3
OJ
lalanine, tyrosine and methionine), and renal tubular dysfunction leading to aminoaciduria
and metabolic acidosis. Prelimina1y diagnosis is made when reducing substances other
,-+
m than glucose are found in the urine. Diagnosis is confirmed by a low level of GAL-1-
X
OJ
PUT in erthyrocytes. Tests include the Beutler test; a widely used fluorescent spot test
3 for galactose-1-phosphate uridyl transferase activity (can use a Guthrie card blood spot).
False negatives n1ay occur after blood transfusion. Other tests include an assay of red
blood cell galactose-1-phosphate level (not affected by blood transfusion) and DNA
analysis (60% of the UK is homozygous for Q188R mutation). Checking the urine for
reducing substances is neither sensitive nor specific; small quantities of galactose are
often found in the urine of patients with liver disease. Also, galactose may disappear
rapidly frorn the urine in patients with galactosaemia. Initial management is i1nmediate
dieta1y withdrawal of galactose; galactose-free milk substitutes are available on prescrip
tion (e.g. infasoy, progestamil). Supportive care n1ay be required. Antibiotics, i.v. fluids
and vitamin K are often necessa1y. Galactose restriction is necessary throughout life to
stop any recurrence of severe toxicity. Early treatment does not, however, prevent
long-term complications (cognitive dysfunction, and gonadal dysfunction in fen1ale
patients). Recent evidence suggests there is an endogenous production of galactose that
may be responsible for the long-term effects.
292
A 12-year-old boy is referred to the growth clinic. His height has fallen from the 90
th
centile to the 3rd centile between the age of 6 and 12 years. He has no signs of s:
.,,
puberty yet. Over the past few months he has had deteriorating school performance ;o
()
and behavioural change. He also complains of paraesthesiae and spasms in his face and ()
arms. While investigations are progressing, he also starts to complain of deteriorating
.,,....
:::r:
vision, and on ophthalmological examination is found to have bilateral cataracts. OJ
r+
Investigations showed: N
Adjusted Ca 0.68 mmol/I
Mg 0.57 mmol/I
P04 3.22 mmol/I
Bone age 7 years
EEG generalised slow wave activity of high amplitude
CT head normal
a. What is the next best investigation?
i. Parathyroid hormone level
ii. Vitamin D levels
iii. Alkaline phosphatase
iv. DEXA bone scan
v. X-ray wrist
b. What other conditions may be associated with this boy's diagnosis?
i. Ectodermal dysplasia
ii. Congenital heart disease
iii. Eczema
iv. Alopecia
v. Addison's disease
vi. Hypothyroidism
vii. Renal osteodystrophy
viii. Cleft palate
293
ANSWERS CASE 7.17
a. i. Parathyroid hormone levels
b. i. Ectodermal dysplasia
D iv. Alopecia
C:
('j)
v. Addison's disease
�
o· This boy has hypoparathyroidism. The cataracts have developed as a result of severe
:l
V'l
OJ
hypocalcaemia. Hypocalcaen1ia is also the cause of his abnormal EEG, and his tetanic
::::, spasms. ECG changes are also likely to occur with severe hypocalcaen1ia, typically a
Q..
prolonged QT interval.
)>
::::,
V'l Parathyroid hormone levels need to be checked to confirn1 the probable diagnosis of
� hypoparathyroidism. In this child they were very low at 0.1 pmol/1. Typical laboratory
�
V'l
findings in hypoparathyroidism are lavv calciun,, raised phosphate, normal or lovv
-+,
0
'""I
alkaline phosphatase, low parathyroid hormone and low vitamin D.
,-+
:::; The hypocalcaemia needs to be slowly corrected. This will require a calcium and
(1)
vitamin D therapy, with careful monitoring for calcium toxicity (nephrocalcinosis, and
z
(1) nephrolithiasis). A suggested scheme is:
�
.,,
0
Acute calcium supplementation with i.v. calcium gluconate 0.3 ml/kg of 10% injec
tion, diluted five-fold and given slowly. Monitor for bradycardia and
3 extravasation
OJ
,-+ • Calcium supplement 1 mmol/kg/day orally
m
X
Al:fucalcidol (1-alpha-hydroA1cholecalciferol) 0.05 µg/kg/day starting dose
OJ Calcitriol (1,25-dihydroA1cholecalciferol) initially 250 ng/day (short-acting therefore
3 will not slavvly accumulate and cause delayed vitamin D toxicity)
Hypomagnesaemia needs correction.
Hypoparathyroidism in childhood is usually autoimmune. It is associated ,vith muco
cutaneous candidiasis and Addison's disease. Other associated conditions are alopecia,
diabetes mellitus and ectodermal dysplasia. When these associations are present, it con
stitutes autoimmune polyendocrinopathy 1 or the APECED syndrome. Antibodies
targeting the calcium sensing receptor can be identified. Patients have concurrent stea
torrhoea and low magnesium levels.
294
Fig 7.18
A 2-week-old baby presented clinically septic. He was born at term, and had been well
until 24 h before admission. Analysis of his CSF showed 285 x 106/I WBC (90%
polymorphs), 1000 x 106/I red blood cells, protein 4.9 g/dl and glucose 1.9 mmol/I.
Subsequent CSF and blood cultures were positive for f. coli, sensitive to cefotaxime,
with which he was treated from admission. After 1 week of treatment he was still
spiking high temperatures, and remained lethargic with poor feeding. A cerebral
ultrasound was performed and is shown.
a. What complication has occurred?
i. Cerebellar coning
ii. Acute hydrocephalus
iii. I ntraventricular haemorrhage
iv. Ependymal cyst
v. Periventricular leukomalacia
b. What further investigations are required?
i. CT scan
ii. lntraventricular tap
iii. MRI
iv. Repeat lumbar puncture
V. ECG
295
ANSWERS CASE 1.18
a. ii. Acute hydrocephalus
b. i. CT scan
0 iv. Repeat lumbar puncture
C
<D
The diagnosis here is neonatal meningitis secondary to E. coli infection. The complica
VI
,r
r+
::::i tion is acute hydrocephalus and probably ventriculitis. Further investigations would
VI
OJ
include a CT scan, repeat lumbar puncture to send CSF for further culture and sensi
tivity, and neurosurgical referral for decompression of the hydrocephalus.
c..
::::i
)> Options include:

:::::i
repeated percutaneous ventricular taps
(I) insertion of a reservoir, e.g. an Ommaya reservoir, through which repeated ven
""'I
VI
tricular taps can be performed and, if desired, intraventricular antibiotics given
-h
0
""'I
percutaneous endoscopic third and fourth ventriculostomies, to encourage CSF flow
r+ and ren10val
::y
(I) ventriculo-peritoneal (VP) shunt
z
(I) Hydrocephalus is an acute complication of meningitis, uncommon beyond the neonatal
� period. The incidence has greatly reduced over the years vvith the use of improved
"Tl
0 antibiotics. Gram-negative organisrn_s are n1ost conm1-only associated with hydrocepha
3 lus formation. The experience of some neurosurgeons is that ventriculostomy has
OJ
r+ decreased the need for a VP shunt by one-third. In this case, his repeat CSF samples
m
>< showed 1600 X 106 /1 WBC (90% polymorphs), 1000 X 106 /1 red blood cells, ,vith
OJ
again a positive culture for E. coli sensitive to cefotaxime indicating a ventriculitis. He
3
undenvent reservoir insertion, then ventriculostornies, but eventually had a VP shunt
insertion.
296
1. Von-Hippel-Lindau syndrome 6. Joubert's syndrome
2.
3.
Lennox-Gastaut syndrome
Abetalipoproteinaemia
7. Niemann-Pick disease
8. West syndrome s:
.,,
::,J
4. Leigh syndrome 9. Neuronal migration disorder (")
5. Marchiafava-Bignami syndrome 10. Multiple sclerosis (")
.,,
:::c
For each of the following case scenarios select the most likely diagnosis from OJ
the list above; �
N
a. A 4-week-old baby presented with intermittent tachypnoea and apnoea since day 1
of life. Episodes were multiple each day and mostly self-resolving, though mild
stimulation would be required occasionally. Associated with the apnoea she would
become cyanosed. She was otherwise well and was feeding orally. She had no
constant oxygen requirement.
The baby was born at full term by normal vaginal delivery. There was no
resuscitation at birth. Family history was negative for congenital abnormalities and
neurological disorders. Examination revealed a non-dysmorphic child with axial
hypotonia and erratic nystagmus and dysconjugate eye movements. The rest of the
neurological examination was normal. MRI showed an absent cerebellar vermis, and
the characteristic "molar tooth" sign on axial images.
b. A 5-year-old girl with "dystonic cerebral palsy" presented with a 4-week history of
respiratory difficulty. Initially this had been associated with a respiratory tract
infection, but over the 4-week period a disordered respiratory pattern had emerged.
She had a normal birth to unrelated parents but was developmentally delayed at the
age of 6 months. At this time her parents had also noted breath-holding episodes
with loss of consciousness. Examination revealed dystonic posture with stiffness and
hyperreflexia of her limbs, truncal hypotonia, fine nystagmus and tremor on
movement. She had pale optic discs, but vision seemed unimpaired. A brain MRI at
this time demonstrated mild atrophy and her condition appeared to be static.
c. A 3-day-old female infant on the post-natal ward had been noted to be feeding
poorly since birth and the midwife is concerned that she was floppy. She had a
couple of twitchy episodes which resolved spontaneously. Her blood glucose had
been normal. Antenatal scans showed polyhydramnios but were otherwise normal.
She is the first child of unrelated Caucasian parents. On examination, she has mild
dysmorphic features including a high forehead with central furrowing, bitemporal
narrowing and bilateral 5th finger clinodactyly. Her weight is on the 25th centile and
her head circumference on the 9th centile. She is centrally hypotonic and has a poor
suck. A cranial USS shows few visible gyri, and an EEG is performed showing
hypsarrthymia.
297
a. 6. Joubert's syndrome
D
C:
(1) Joubert's syndrome is a clinical presentation of episodic apnoea/tachypnoea with nys
Vl
tagmus, ataxia, developmental delay and cerebellar vermian dysgenesis. MRI is charac
o·
,-+
:::,
teristic and differentiates it from Dandy-Walker malformation. Abnormal breathing
Vl
!l)
pattern has been reported in the majority of cases and occurs in both REM and non
6- REM sleep as ·well as whilst awake. The exact aetiology is unknown. A proportion of
patients will have retinal dystrophy. Some patients are severely affected and die in
)>
:::, infancy. The majority of those who survive have delayed development and learning
difficulties.
(1)
'""I
Vl
-+-, b. 4. Leigh syndrome
0
'""I
,-+ Leigh syndrome is a progressive neurodegenerative condition of infancy and childhood.
::;
(1) It is thought to result from. a severe failure of oxidative n1etabolis1n ,vithin n1itochondria
z
(1)
of the developing brain. Inheritance can be X-linked recessive or autosomal recessive
depending on the defect responsible. The characteristic synm1etric necrotic lesions dis
.,,
0
tributed along the brainstem, diencephalons and basal ganglia are readily visible on
3
OJ
MRI or CT, but n1ay not be present on scans in early life. The clinical presentation
and course may va1y considerably but syn1ptoms often include signs of brainstem or
,-+
m basal ganglia dysfunction. Develop1nental delay and regression are prominent clinical
>< features of this disorder. The clinical course can follow a stepwise deterioration with
OJ
3 sorne recovery of developn1ental skills between episodes of regression or a slowly pro

gressive decline. Investigations include cerebral imaging, muscle biopsy and CSF lactate
(may be raised, but normal levels do not exclude the diagnosis).
c. 9. Neuronal migration disorder

Neuronal migration disorders are malformations of cortical development, and are highly
associated with epilepsy, developmental delay and 1nental retardation. Associated fea
tures may include autism, learning difficulties, hypotonia and spasticity. In sorne cases,
there is global neurodevastation and failure to thrive. This baby had Miller-Dieker
syndrome, a neuronal migration disorder, as suggested by her clinical features and
lissencephaly (smooth brain) ,vhich can be confirmed on MRI. These patients need to
be managed by a multi-disciplinary team. They often fail to thrive, and require gas
trostonry feeding. A paediatric neurologist should be involved if seizures are intractable.
Death usually occurs before 2 years of age. A deletion of 17p13.3 has been documented
in the majority of cases. Hypsanythmia refers to a chaotic EEG ,vith high-amplitude
asymmetrical non-synchronous spike, polyspike and slow waves, with an irregular
background activity. Treat1nent of hypsarrythmia is difficult and resistant to most anti
epileptic drugs. Recently, vigabatrin has been used successfully, but it can cause visual
field defects ,vhich are irreversible.
298
Fig 7.20
You have been called to see a newborn baby aged 40 min on the neonatal unit. Born
at 34 weeks' gestation with an insignificant antenatal history, he was put on CPAP
because of mild respiratory distress. The nurses report that the oxygen saturation had
dropped from 95% in air to 78% in 45% oxygen. On examination, the respiratory rate
is 60/min with some intercostal recession and reduced air entry on the left. The urgent
CXR is shown.
i. Left-sided pneumothorax
ii. Left-sided pneumatocoles
iii. Congenital pulmonary emphysema
iv. Congenital cystic malformation of the lung
v. Left-sided congenital diaphragmatic hernia
vi. Loculated empyema
299
ANSWER CASE 7.20
v. Left-sided congenital diaphragmatic hernia
D The CXR shows fluid levels in the left hen1ithorax, an abnormal position of the
c::
(I) nasogastric tube, and n1ediastinal shift to the right all consistent with a diagnosis of
� left-sided diaphragmatic hernia.
o·
:::l
Vl Congenital diaphragmatic hernia (CDH) occurs in one of every 2000-4000 live births
ru and accounts for 8'¼1 of all major congenital anomalies. The risk of recurrence of isolated
:::s
Q.. CDH for future siblings is approximately 2%. Infants may have an antenatal history of
:.t> polyhydranmios and rnost commonly present with a history of cyanosis and respiratory
:::l
distress in the first minutes or hours of life, although a later presentation is possible.
� They frequently exhibit a scaphoid abdomen.
�
Vl
-+,
0
"""I
,-+
::,
(1)
z
(1)
�
.,,
0
3
OJ
,-+
m
><
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3
300
s:
;:c,
(")
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(")
I
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;::i
N
(c)
Fig 8.1
This 5-year-old boy presented with a history of marked snoring every night, shortness
of breath on exertion and excessive day-time sleepiness. He has been diagnosed with
Prader-Willi syndrome.
a. What investigation was performed (Fig. 8.1.c)?
i. Cardiotocograph
ii. Sleep study
iii. Exercise ECG
iv. Spirometry
v. Pulse oximetry
b. What does the result show?
SELECT THE BEST ANSWER ONLY
i. REM sleep pattern
ii. Oxygen desaturations
iii. Obstructive airways disease
iv. Right heart strain
v. Obstructive sleep apnoea
c. What other investigations would you request for this patient?
i. CT head
ii. ECG
iii. Bone scan
iv. Echocardiogram
v. Glucose tolerance test
303
ANSWERS TO CASE
a. v. Pulse oximetry
b. v. Obstructive sleep apnoea
D c. ii. ECG
C
(I)
iv. Echocardiogram
!!l
o·
:::::; Prader-Willi syndron1e is inherited by uniparental maternal disomy on chromoso1ne
Vl
OJ
15. The characteristic features include: fetal and infantile hypotonia, small hands and
:::::; feet, post-natally acquired obesity through voracious appetite, cryptorchidism, n1icro
0..
penis and mild mental retardation. Excessive daytirne sleepiness occurs in approximately
)>
:::::; 50-75% of patients with Prader-Willi syndro1ne. Children with this syndrome have
�
(I)
been shown to have increased nurnber of apnoeas, a decreased nadir of o:;-,._1gen satura
"""I
I.fl
tion, and decreased respiratory response to hypercapnia during quiet sleep. Obstructive
-+, sleep apnoea is one important factor related to subsequent daytime sleepiness, ,vorsened
0
"""I by obesity. An additional central disturbance sleep mechanism (hypothalamic dysfunc
,-+
::J"" tion) is thought to be present.
(I)
z InV€:stigations include pulse oximetry, which in this example shmvs episodes of severe
(I)
� desaturations down to around 65% during REM sleep (with a corresponding rise in
.,,
0
heart rate). This pattern is consistent with obstructive sleep apnoea .
3
OJ
An ECG is done to look for right ventricular hypertrophy, and an echocardiogram_ to
,-+ exclude right heart failure.
m
>< Treatments are sym_ptomatic. Adenotonsillectomy n1ay be beneficial, but does not
OJ
3 consistently cure all symptoms. Weight loss should be encouraged. CPAP may be used
during sleep, but, in severe cases, an artificial airway may be required, e.g. nasopha
ryngeal tube or tracheostomy. Diuretics may be needed to relieve right heart failure as
an adjunctive therapy.
304
An infant was born at full term following a normal pregnancy to a 24-year-old
primigravida. No problems followed delivery and the infant was discharged home at
24 h of age breast feeding normally. His mother, a nurse, was highly motivated to
s:
:::cl
(')
breast feed with no supplemental feeds. He was re-admitted at 6 days of age with '"tl
(')
severe jaundice. He had had two bowel movements and no vomiting. He has problems ::r:
latching on because he is always sleepy. On examination, he is lethargic, has a sunken '"tl
OJ
anterior fontanelle and dry mucous membranes, but is pink with normal respiratory rate ::l
and a clear chest. There are no cardiac murmurs. A septic screen and some initial blood N
tests show:
Na 170 mmol/I
I< 4.2 mmol/I
Cl 130 mmol/I
Ca 2.2 mmol/I
Total bilirubin 425 µmol/I
Hb 22 g/dl
wee14 x 10 9/J
a. What is the other most useful measurement?
i. Serum osmolality
ii. Urea
iii. Urine osmolality
iv. Weight of baby
v. Blood gas
b. What is the most likely cause of the biochemical abnormalities?
i. Renal dysfunction with polyuria
ii. Diabetes insipidus
iii. Intake of over-concentrated feeds
iv. Inadequate breast feeding
v. Cystic fibrosis
c. Which of the following are likely to be involved in treatment?
i. i.v. normal saline
ii. i.v. 10% dextrose
iii. Oral rehydration with water
iv. Oral rehydration with electrolyte solution
v. i.v. bolus of normal saline
vi. Oral rehydration with milk
vii. i.v. 10% dextrose with electrolytes
305
ANSWERS TO CASE 8.2
a. iv. Weight of baby
b. iv. Inadequate breast feeding
c. vi. Oral rehydration with milk
vii. i.v. 10% dextrose with electrolytes
Weighing the infant reveals that he has lost 25% of his birthv.reight indicating that the
Q)
hypernatraemia and hyperbilirubinaemia are due to dehydration.
:::::l
Cl. It is likely that this baby's hypernatraemic dehydration is due to inadequate breast 1nilk
)> intake. Despite its proven advantages, there are complications of breast feeding. Loss
:::::l
of water from insensible losses through the skin and lungs in the absence of concomitant
�
(I) sodium loss ,vithout adequate intake may result in this picture.
-h This infant had hypernatraemic dehydration due to inadequate intake secondary to a
Q poor breast milk supply. The most important treatment is slow rehydration. The fluid
r+
::::, deficit is calculated from the weight loss and replaced over 48 h to prevent too rapid
(I)
a fall in the serum_ sodium concentration; i.v. treatment is given as 10% dextrose with
z
(I) normal sodium_ content (3-4 1mnol/kg/day). Ideally, breast feeding should be continued
�
.,,
0
but additional support and monitoring will be required. As the infant is rehydrated,
the sermn bilirubin will also fall back into the norn1al range, but phototherapy should
3
OJ
also be used to help decrease the bilirubin concentration.
r+
m
><
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3
306
A 6-year-old boy, who has been followed up for a number of years for poor growth,
was found to have pancytopaenia on a routine blood test (Hb 8.3 g/dl, wee 2.4 x
s:
10 9/1, neutrophils 1 .1 x 10 9/I and platelets 55 x 10 9/1). Additionally, he had small :::0
thumbs and three small cafe-au-lait spots on his trunk. He had previously had a ()
-0
bilateral orchidopexy. With treatment, his haematological parameters returned to ()
I
normal. -0
a,
Six months later, he developed a vesicular, painful rash in a dermatomal distribution in �
the right lumbar area. N
a. Suggest the underlying diagnosis, and a way of confirming it:

i. Holt-Oram syndrome
ii. Pseudohypoparathyroidism
iii. Hypoparathyroidism
iv. Fanconi's anaemia
v. Neurofibromatosis
b. Name one important long-term complication:
i. Splenomegaly
ii. Aplastic anaemia
iii. Malignancy
iv. Neurological manifestations
v. Pneumococcal infection
307
ANSWERS 8.3
a. iv. Fanconi's anaemia
b. iii. Malignancy
Pancytopaenia with sn1all thumbs, cafe-au-lait spots and poor growth suggests a diag
nosis of Fanconi's anaemia. This is an autosomal recessive disorder of DNA repair,
with a high risk of malignancies, and renal dysfunction. Without treatn1ent, the average
OJ
life span is approximately 15 years. Bone marrow transplantation is curative if successful,
::l but imnrnnosuppression makes overwheln1ing varicella infection a serious risk.
c..
)> Confirmation of the diagnosis of Fanconi's anaemia is made by a chron10some
::l
V'l fragility test.
C1)
V'l
-+,
0
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C1)
z
C1)
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0
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3
308
s:
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()
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N
Fig 8.4
A 9-year-old girl is referred from the ophthalmology clinic. Her visual acuity is 6/12 in
the right eye and 6/18 in the left eye. Her optic discs are pale. She was born at 31
weeks' gestation the first of twins. She required ventilation for the first week and
developed an intra-ventricular haemorrhage with secondary hydrocephalus requiring a
shunt at 5 months of age. Her fine motor skills are slightly behind those of her peers
and sister but she attends mainstream school. A CT brain scan was arranged (Fig. 8.4).
What abnormality is shown?
i. Right sided mass in posterior ventricle
ii. Cystic periventricular leukomalacia
iii. Hydrocephalus
iv. Left intraventricular haemorrhage
v. Non-cystic periventricular leukomalacia
309
ANSWER TO CASE 8.4
iv. Non-cystic periventricular leukomalacia
The CT shows periventricular leukomalacia (PVL) or white n1atter loss in the posterior
temporal and parietal lobes, in this case non-cystic.
The child's reduced visual acuity is likely to be a complication of her preterm birth,
although there are many theoretical causes. This child may have had retinopathy of
Ql
:J
prematurity in the past, or her pale optic discs may represent optic atrophy secondary
a. to hydrocephalus. Periventricular leukomalacia n1ay also be the cause of her reduced
)> vision since developn1ent of neonatal vision is subcortically n1ediated and lesions affect
:J
Vl ing the optic radiations, especially cystic PVL, niay subsequently affect visual acuity.
(I)
"""I
Vl
These appearances on the CT scan could also be associated with cerebral palsy
- (especially spastic diplegia) and other visual problems such as visual field defects, non
0
"""I paralytic strabisnms, oculmnotor dyspraxia, optokinetic nystagmus and reduced bino
r+
::J'" cular visual acuity.
(I)
z
(I)
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0
3
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r+
m
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310
A 5-year-old girl presented with pubic hair development. She had been born at 36
weeks' gestation weighing 1800 g. She was otherwise healthy. On examination her
height was on the 90th centile. She had acneiform lesions on the forehead. There was
no breast development; there was sparse pubic hair and some cliteromegaly.
Her serum electrolytes were: Na 137 mmol/I, K 4.0 mmol/I, urea 4.4 mmol/I and
creatinine 52 µmol/1.
.,,
OJ
-:
r+
a. What possible diagnoses should be considered? N
i. Precocious puberty
ii. Congenital adrenal hyperplasia
iii. Testicular feminisation syndrome
iv. Cushing's syndrome
v. Craniopharyngioma
b. What additional investigations are indicated?
i. 17-OHP
ii. Urinary steroid profile
iii. LH/FSH
iv. CT head
v. Serum testosterone
311
TO CASE 8.5
a. ii. Congenital adrenal hyperplasia
iv. Cushing's syndrome
b. i. 17-0HP
ii. Urinary steroid profile
These signs are due to excess androgen production. Causes include congenital adrenal
Ill
hyperplasia, adrenal tumour, ectopic androgen-secreting tumours (e.g. teratoma) and
:::J Cushing's syndrorne. This girl is showing pseudo-precocious puberty, i.e. there is a
0...
lack of consonance in pubertal developn1ent. The clitoral enlargement makes simple
)>
:::J
VI
premature adrenarche unlikely.
ro Investigations should include 17-hydroA7progesterone, cortisol (0900 and 2400), urinary
'""'I
VI steroid profile, ultrasound of adrenals and ovaries, X-ray of left wrist for bone age, and
-
0
'""'I
renin and aldosterone.
r+
:::J" In this case, the urinary steroid profile was diagnostic, showing the characteristic pattern
ro
of 21-hydroA7lase deficiency, with increased metabolites of 17-hydroA7progesterone
z
ro and an increase of androgen n1etabolites relative to cortisol metabolites. One quarter
.,,
0
of children with 21-hydroA7lase deficiency are non salt-vvasting. The bone age in this
girl was characteristically advanced at 8.1 years.
3Ill Treatment is with hydrocortisone, initially 20 mg/n-i2 /day, in three divided doses. The
r+
m dose is adjusted according to subsequent profiles of 17-hydroA7progesterone and assess
>< ment of growth and bone age. The child niay need to be seen by a paediatric urologist
OJ
3 and may require cliteroplasty.
Inheritance of congenital adrenal hyperplasia is autosomal recessive, therefore both
parents are carriers. The girl had an elder sister whose urine steroid profile was norn1al.
No further children were planned (antenatal diagnosis and treatment of affected fern.ale
pregnancies with dexamethasone can be offered).
312
A previously fit and well 14-year-old girl presented with a 7-week history of malaise
and lethargy, associated with constipation and abdominal pain. On assessment, she was
unwell and pale. Her abdomen was distended and tender. She had two small aphthous
s:
:::0
()
ulcers in her mouth and three ulcerated skin lesions over both elbows. Investigations ""Cl
()
showed a microcytic anaemia and an elevated ESR and CRP. Her abdominal radiograph
showed faecal loading. ""Cl
OJ
""'I
r+
a. What is the most likely diagnosis? N
i. Irritable bowel syndrome
ii. Lymphoma
iii. Crohn's disease
iv. Wegener's granulomatosis
v. Ovarian carcinoma
vi. Hypothyroidism
b. What further investigations are required?
SELECT THE TWO BEST ANSWERS
i. Barium meal and follow-through
ii. LFTs
iii. CT abdomen
iv. White cell scan
v. Thyroid function tests
vi. Autoimmune screen
vii. Bone marrow aspirate
313
ANSWERS TO CASE 8.6
a. iii. Crohn's disease
b. i. Barium meal and follow-through
.0
C: iv. White cell scan
())
Vl
o·:J The onset of Crohn's disease is often insidious. Cramping abd01ninal pain, weight loss
r+
and diarrhoea are common manifestations. The patient niay also have fever or constipa
Vl
DJ
tion. There are many extra-intestinal manifestations such as polyarticular arthritis,
:J pericholangitis, hepatitis, sacroileitis, skin lesions and iritis which may precede gastroin
0..
testinal disease. Perianal disease n1ay produce fissures, fistulas or abscesses. The pathol
)>
:J ogy of Crohn's disease involves non-caseating granulon1a formation in a discontinuous
� pattern (skipped lesions) and transmural inflammation in the ileum and colon. The
�
())
Vl differential diagnosis includes chronic bacterial or parasitic infection such as giardiasis
-+, and yersinia enterocolitica.
�0
r+ Investigations that should be pe1formed include a barium meal and follow-through, a
::,
()) colonoscopy and a white cell scan.
z
())
�
.,,
0
3
CJ
r+
m
X
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3
314
Fig 8.7
This baby was born at 35 weeks' gestation by elective Caesarean section. Severe
respiratory failure was evident from birth and ventilation was required. The CXR done
at 1 h of age is shown.
i. Cystic fibrosis
ii. Left pneumothorax
iii. Staphylococcal sepsis
iv. Cystic adenomatoid malformation of the lung
v. Left diaphragmatic hernia
315
ANSWER TO CASE 8. 7
iv. Cystic adenomatoid malformation of the lung
.0 This baby has a cystic adenomatoid malformation of the left lung. The main differential
C
diagnosis is a left diaphragmatic hernia. The key to making the correct diagnosis is
�
(I)
noting that the ston1ach and bowel are in the normal position. If in doubt, for instance
o·
:::s
,vhen the stornach has no gas in it, a sn1all amount of contrast n1aterial can be inserted
V,
ID into the stomach to define its position.
:::s
a.. If the baby is asympton1atic, the lesion is usually removed electively when the child is
)> older.
:::s
V,
(I)
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V,
--+,
0
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,-+
::,
(I)
z
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0
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316
A baby girl was born at 35 weeks' gestation to consanguineous parents following
polyhydramnios and symmetrical intrauterine growth retardation in pregnancy. s:
�
Obstetric history: One previous child was born at term with no problems; the mother n
"'CJ
had had three miscarriages for no known reason. n
:::c
After birth there was an uneventful initial course, but at 8 days of age she had lost "'CJ
OJ
15% of her birth weight. She had been tolerating feeds well and there had been no
diarrhoea or vomiting. Examination, apart from symmetrical growth retardation, was N
normal including blood pressure. Blood urea, creatinine and electrolytes were as
follows:
Na 113 mmol/I
K 1.8 mmol/I
Cl 60 mmol/I
Bicarbonate 38 mmol/I
Urea 10.1 mmol/I
Urinary Cl 32 mmol/I
i. Renal tubular acidosis type II
ii. Neonatal Bartter syndrome
iii. Acute tubular necrosis
iv. Congenital adrenal hyperplasia
v. Acute renal failure
vi. Renal tubular acidosis type I
317
ANSWER TO CASE 8.8
ii. Neonatal Bartter syndrome
The biochemical abnormality is a hypokalaemic hypochloraen1ic n1etabolic alkalosis
with hyponatraernia. Conditions associated with hypokalaemic hypochloraemic 1neta
bolic alkalosis and normal blood pressure can be differentiated on the basis of urinary
chloride excretion. In those with extra-renal losses of chloride (gastrointestinal
or sweat), the normal kidneys respond by reducing urinary chloride excretion
(<10 mmol/1). In this situation, a high urinary chloride excretion (>20 nunol/1) sug
gested a renal loss of chloride and therefore either Bartter-like syndrom.e or diuretic
use/abuse. Detection of diuretics in the urine, if required, helps establish the difference.
U&E should be sent to confirm the renal loss of electrolytes. In this case, there was
also increased urinary sodium, potassium. and calcium. A capillary gas should be checked
to confirm metabolic alkalosis (demonstrated by the high bicarbonate). Renin and
aldosterone would be elevated. The hypokalaemia prom.ates aldosterone secretion and
increased prostaglandin production promotes secretion of renin and further increased
aldosterone production.
Bartter syndrome represents a closely related set of renal tubular disorders characterised
"T1 by hypokalaemia, hypochloraemia, metabolic alkalosis and hyperreninaemia with normal
0
3
CJ
BP. The underlying renal abnormality results in excessive urinary losses of sodium,
potassium and chloride. Bartter syndrome can be divided into neonatal and classic
r+
m
types.
><
CJ Neonatal (or pre-natal) Bartter or Hype1prostaglandin E syndrome (HPGES) is characterised
3 by polyhydranmios due to intrauterine polyuria, premature delivery and growth retar
dation. They often have specific facies: a triangular-shaped face, prominent forehead,
large eyes, protruding ears and a drooping mouth. BP is norm.al. Life-threatening epi
sodes of fever and dehydration during the early weeks of life may occur, due to massive
neonatal polyuria (urine output up to 50 rnl/kg/h). The essential features include
hypokalaemic hypochloraemic metabolic alkalosis, nonT1al blood pressure, increased
urinary potassium. and chloride loss and elevated plasma renin and aldosterone. Defec
tive maximal concentration and dilution of urine, hypercalciuria, hypomagnesaemia,
osteopaenia, increased urinary prostaglandins are also present.
Classic Bartter syndrome. Patients have a history of maternal polyhydramnios and prema
ture delivery. Sym.ptoms in classic Bartter syndrome include polyuria, polydipsia, vomit
ing, constipation, salt craving, failure to thrive, and in late childhood, fatigue, muscle
cramps, recurrent carpopedal spasms. There ni.ay be developmental delay and n1.inimal
brain dysfunction. Facial appearance may be similar to that of neonatal Bartter, but this
is infrequent. Genetic mutations (chromosome15q) lead to defective transepithelial
chloride transport across the thick ascending limb (TAL) of the loop of Henle. The
resultant decrease in sodium chloride reabsorption in the TAL will reduce medullary
hypertonicity, perhaps explaining the concentrating defect. With the markedly increased
salt delivery to the distal nephron, sodium is exchanged for potassium. Increased sodium
reabsorption via the epithelial channel, coupled with increased potassium and hydrogen
ion secretion in the collecting tubule ,vould cause hypokalaemic metabolic alkalosis.
The markedly increased salt delivery to the distal nephron causes salt wasting, volume
contraction and stimulation of the renin-angiotensin-aldosterone axis. In1.paired elec
trogenic chloride transport in the TAL also inhibits the voltage drive, paracellular rea
bsorption of calcium and magnesium and thus causes hypercalciuria and magnesuria.
Hypokalaemia, chronic volume contraction and elevated levels of angiotensin, kal
likrein, kinins and vasopressin all stimulate prostaglandin E2 production. This and
chronic volume contraction probably cause the resistance to the pressor effects of
angiotensin or catecholamines and this may explain the normal blood pressure in the
presence of elevated renin levels.
31..8
A 4-year-old-boy was referred to outpatients after two generalised afebrile tonic clonic
seizures lasting up to 10 min. A 6-month history of frequent falls was elicited which
were causing concerns at nursery and were used as the explanation for his bruises.
These falls would happen several times a day, his eyes would roll back and he would
fall to the ground for up to 4 min with no aura or warning. In between falls, he was
well. His past medical history included a minor head injury.
He was delayed in reaching his milestones but there was no history of regression.
Examination revealed microcephaly and multiple bruises. An EEG showed a slow
polyrhythmical background with high-voltage irregular delta waves in the anterior
region, and frequent bursts of generalised irregular spike and wave activity. Upon
review in outpatients, he had developed myoclonic seizures.
i. Wiskott-Aldrich syndrome
ii. Lennox-Gastaut syndrome
iii. Rett's syndrome
iv. West syndrome
v. Angelman syndrome
vi. Acute demyelinating encephalomyelitis
b. Which anticonvulsant would you start?
i. Vigabatrin
ii. Sodium valproate
iii. Carbamazepine
iv. Phenobarbitone
v. Lamotrigine
319
ANSWERS TO CASE 8.9
a. ii. Lennox-Gastaut syndrome
b. ii. Sodium valproate
Lennox-Gastaut syndrome is a severe forrn of childhood epilepsy characterised by
multiple seizure types (tonic, atonic/ drop attacks, rnyoclonic, atypical absences), devel
opmental delay, behavioural disturbances and a characteristic EEG. The incidence is
CJ one in 10 000. It usually develops between the ages of 3 and 5 years. Sixty per cent
:::s of children with the syndrome have neurological symptoms prior to the onset of sei
Q..
zures, and the majority have intellectual impairment at diagnosis. Behavioural distur
)>
:::s
V'l
bances such as poor social skills and attention-seeking behaviour are common. In 30%
of cases, there is a history of infantile spasn1s. The prognosis is usually poor. Nearly
(I)
'""I
V'l
80% continue with seizures in adult life, and only 17% can lead independent lives.
-h Sodium valproate is the initial anti-epileptic medication of choice, as carbamazepine
0
'""I may increase the frequency of myoclonic seizures. Two-thirds of patients will be resist
r-+
::; ant to conventional therapy.
(I)
z
(I)
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0
3
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3
320
Fig 8.10
A 13-year-old girl was referred to the endocrine clinic, as her parents were concerned
about her short stature. She was in good health and was developmentally normal. Her
parents described her appetite as poor but her diet was said to be healthy. On
examination, she had a few pigmented naevi and low set ears but had no other
specific dysmorphic features. She was noted to have an ejection systolic murmur grade
2/6, maximal at the left sternal edge. Her blood pressure was 100/60, and her
peripheral pulses were normal. Her growth chart is shown. Her mid-parental height was
169 cm. She was pre-pubertal.
What initial investigations should be performed?
i. CXR
iii. Bone age
iv. FBC
v Coeliac screen
\/i. Karyotype
vii. CT brain
viii. LH/FSH
321
iii. Bone age
.0
C
vi. Karyotype
(I)
�
o·
:::s
Investigations should include a karyotype, thyroid function tests, U&E, blood glucose,
LFTs, FBC, ESR, calcium, phosphate, ALP, bone age, echocardiography, and possibly
VI
Q)
a coeliac screen.
:J
0.. The diagnosis in this girl was Turner's syndrome. She has a karyotype of 45 XO, with
)> no evidence of mosaicisn1. The diagnosis should be considered in any girl with unex
:::s
plained short stature whether or not there are any suggestive phenotypic features.
�
(I) Turner's syndrome occurs with a frequency of approximately 1 in 2500 live births.
"""I
VI Two-thirds of cases have the 45 XO genotype, the rernaining one-third have a n1osaic
-+,
0
"""I
chromosome pattern or loss of only a part of the X chromosome. Twenty-four per
,-+ cent have cryptic Y chromosome material. In girls with Turner's syndron1e it is impor
:::s
(D tant to obtain a cardiology opinion, whether or not they have signs suggestive of an
z underlying cardiac problem. There is a recognised mortality from cardiovascular mal
(D
� formations (coarctation, aortic dilatation, dissection or rupture) in young adulthood.
,,
0
3
Q)
,-+
m
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3
322
A 12-year-old girl presented to the A&E department. Three days earlier she slipped on
ice and fell on her left arm. Then she complained of discomfort in her elbow and wrist
but she had no limitation in function. Her parents managed her with simple analgesia.
She complained of persisting pain in her left arm. Additionally, she described numbness
of her thumb and that her arm was weak. Examination showed a mottled arm with
diffuse swelling distal to the elbow. Her forearm and hand felt cool and she
demonstrated reduced sensation to light touch from above the elbow. Forearm power
appeared reduced and her pain was aggravated during examination.
What is the likeliest diagnosis?
i. Ulnar nerve dysfunction
ii. Compartment syndrome
iii. Reflex sympathetic dystrophy
iv. Radial nerve dysfunction
v. Supracondylar fracture with associated peripheral neuropathy
vi. Inflammatory mononeuritis
323
ANSWER TO CASE 8.11
iii. Reflex sympathetic dystrophy
Reflex sympathetic dystrophy (RSD), also known as complex regional pain syndrome
(CRPS), is a clinical diagnosis, but X-rays, Doppler studies and bone scintigraphy are
perhaps the most appropriate investigations to rule out other pathologies. Treatment
involves firm_ reassurance supported by intensive physiotherapy, perhaps augmented by
n,
simple analgesia. Normal use of the affected limb should be strongly encouraged.
� lnunobilising the limb in response to discomfort is unhelpful and may exacerbate the
a.
condition. Underlying psychological factors rnay be involved, so referral for child and
)>
:::J
Vl
family psychiatry evaluation should be considered. RSD/CRPS appears less common
in children than in adults, but can cause significant morbidity. The diagnosis can be
....
<D
Vl
made in the context of a history of trauma to the affected area, with pain and n10bility
-+, disturbance disproportionate to the initial injury. Delayed recognition means that niany
0
.... children undergo extensive investigations to rule out a wide range of possible underly
r+
::r ing conditions. Any skin stimulation, such as water in a shower, may be perceived as
<D
painful (allodynia). Other features include:
z
<D Syrnpathetic disturbance - changes in skin temperature, increased sweating, colour
� changes (rnottling/pallor/blue) due to vasornotor changes
-r,
0 Swelling - diffuse oedema often localized to the painful area
3OJ Movement disturbance - from pain, stiffoess and true difficulty in initiating muscle
r+ n1oven1ent
m Changes in tissue gwwth (dystrophy)
><
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3
324
An 11-year-old girl was admitted after 5 days of intermittent frontal headache, which
had become more severe, and woken her at night. It usually came on after school, but
sometimes in the morning. She had suffered no injury and had not been febrile. Over
the last couple of days, there was associated visual disturbance but no other symptoms.
Her past history included severe asthma, requiring long-term inhaled steroids, and short
stature, with bone age delay. Anterior pituitary function testing, including an insulin
tolerance test, had shown growth hormone insufficiency, a pre-pubertal LHRH
response, a good cortisol response, and normal baseline thyroid function. Cranial MRI,
to exclude a tumour, was normal. Growth hormone had therefore been started.
Examination demonstrated no meningism, and no focal neurological signs. Visual fields,
acuity and colour vision were all normal. However, she had papilloedema.
Lumbar puncture revealed pressure of 24 cm of water, no white cells, two red cells,
protein of 15 mg/di and glucose of 4 mmol/I.
i. Craniopharyngioma
ii. Viral encephalitis
iii. Subacute sclerosing panencephalitis
iv. Acute demyelinating encephalitis
v. Benign intracranial hypertension (BIH)
325
TO 8.12
iii. Benign intracranial hypertension (BIH)
BIH (also known as pseudotumour cerebri) is characterised by signs and symptoms of
increased intracranial pressure with no evidence of underlying systemic causes. Symp
toms include headache, nausea and von1iting, blurred vision and diplopia. Loss of vision
is a serious complication. The diagnosis is suggested by the presence of papilloedema,
a sixth nerve palsy, and a raised opening CSF pressure (with no ventricular
dilatation).
The aetiology of the increased CSF pressure is not known. Theories include obstruc
tion to the flow of CSF at the arachnoid granulations, an increased rate of CSF forma
tion, changes in the brain parenchym.a and blood vessels, obstruction to venous outflow
at the superior sagittal sinus and a reduced ability of the subarachnoid space to expand.
Initial management involves removing CSF by lurn.bar puncture to bring pressure below
20 cm..
Many causes have been implicated in BIH: endocrine (e.g. Addison's, hypothyroidism,
hyperthyroidism, hypoparathyroidism); drugs (e.g. vitamin A, retinoids, tetracyclines,
thyroxine, growth hormone, corticosteroids [and their withdrawal], nitrofurantoin and
-n
0 lithium); viral infections; Lyme disease; iron deficiency anaemia; trauma; and idiopathic
3OJ (the rnost common).
r-+
m
Further investigations are thus needed to elicit a cause: MRI and magnetic resonance
><
OJ venogram are appropriate to exclude an intracranial venous sinus thrombosis. Other
3 investigations may include: thyroid function tests; auto-irnmune profile; immunoglobu
lins; rheumatoid factor; antineutrophil cytoplasmic antibody; angiotensin converting
enzyme; CSF oligoclonal bands; Lyme disease and viral serology.
BIH is usually self limiting. Once the CSF pressure has been reduced, any offending
drugs should be discontinued. For sym.ptomatic control, intracranial pressure can be
reduced by: daily lumbar puncture \Vith CSF drainage, or large doses of acetazolamide
+/- loop diuretic. The role of steroids is controversial. If symptoms are unremitting,
or there is ongoing visual impairment, then a surgical lumbo-peritoneal shunt or optic
nerve fenestration may be required, as infarction of the optic nerve can occur. Notable
clinical features n1.ay include a sixth nerve palsy, and partial or complete monocular
visual loss - the only serious neurologic sign. The normal blind spots are commonly
enlarged.
326
A 9-year-old girl presented with a 2-week history of polyuria and polydipsia. She
appeared well on admission and the only abnormality to find on examination was a
smooth, non-tender goitre. Her blood sugar was 17 mmol/I and she was commenced
on subcutaneous insulin. Her thyroid tests showed:
TSH 0.2 miu/I
Free T4 31.9 pmol/I
Free T3 1O pmol/I
N
a. What is the most likely cause of her thyroid problem?
i. Hashimoto's thyroiditis
ii. Grave's disease
iii. Pendred's syndrome
iv. De Quervain's thyroiditis
v. Secondary hypothyroidism
b. What other autoimmune conditions may be associated with diabetes
mellitus?
i. Addison's disease
ii. Gastric autoimmunity
iii. The polyglandular autoimmune syndromes
iv. Dermatomyositis
v. Autoimmune hepatitis
vi. Systemic lupus erythematosus
327
a. i. Hashimoto's thyroiditis
b. i. Addison's disease
ii. Gastric autoimmunity
iii. The polyglandular autoimmune syndromes
Although she currently has biochemical hyperthyroidism, she is likely to become
Q)
hypothyroid secondary to chronic thyroiditis. Autoimmune thyroid disease is the most
::, common autoimmune disease occurring in families with IDDM, and Hashimoto's
0..
thyroiditis is the most common underlying diagnosis. Thyroid microsomal antibodies
)>
:J are present in about 20% of diabetic children less than 16 years of age. In antibody
positive subjects, approximately 7% will become hypothyroid; 1% will suffer from
V'l Grave's disease.
-+,
0
..., Associated autoimmune diseases are relatively common in children with IDDM, par
r+ ticularly in children who have HLA-DR3. Some conditions may precede the onset of
:::,
(1) diabetes; others develop later. The following are associated autoimmune diseases:
z Hypothyroidism: 2-5% of children with IDDM
(1)
Hyperthyroidism: 1% of children with IDDM
"Tl • Addison's disease: <1% but life-threatening (may reduce insulin requirement), diag
0
3
Q)
nosis may be suspected when growth velocity falls off, or when an individual
develops a marked sensitivity to insulin, with frequent episodes of hypoglycaemia,
r+
m which often precedes classical markers of Addison's disease
>< Coeliac disease, such as increased pigmentation or electrolyte disturbances
OJ
3 Necrobiosis lipoidica: 1-2% of children with IDDM

Parietal cell antibodies (PCA) are present in approximately 10% of children with dia
betes, but rarely progress to clinical disease. However, achlorhydria is not unconm1on
in PCA-positive diabetic children and may lead to iron deficiency.
Polyglandular autoinm1-une syndromes present in three types:
Type I: rare and presents in childhood, it usually comprises mucocutaneous candi
diasis, hypoparathyroidism and primary adrenal insufficiency.
Type II: most common and defined as primary adrenal insufficiency with either
autoinmmne thyroid disease or type I diabetes mellitus occurring in the same
individual (prima1y hypogonadism, myasthenia gravis, and coeliac disease also
occur).
Type III: the co-occurrence of autoimmune thyroid disease with two other autoim
mune disorders, including IDDM (type I), pernicious anaemia or a non-endo
crine, organ-specific, autoinunune disorder in the absence of Addison's disease.
328
A 7-month-old girl of consanguineous parents was admitted with a 48 h history of cold
symptoms and increasing respiratory difficulty. On examination, oxygen saturation was
96% in air and there was mild wheeze. Nasopharyngeal aspirate for respiratory
syncytial virus was positive. Overnight, her respiratory rate increased to 94/min. She
looked tired and dehydrated. A trial of bronchodilator was unhelpful. Further
investigations revealed:
Hb 11.1 g/dl
WBC 38.3 x 109/I (neutrophils 20.8 x 109/1, lymphocytes 12.3 x 109/I)
CXR mild hyperinflation
Capillary blood gas (pH 6.932, pO2 6.81 kPa, pCO 2 2.01 kPa, standard bicarbonate
3.0' mmol/I, base excess -28.4)
Serum ammonia 51 µmol/I (normal range 21-4 7 µmol/I)
Serum lactate 11.5 mmol/I (normal range 1.0-1.8 mmol/I)
Blood glucose 2 2 mmol/1.
;
a. What is the most likely cause of this child's deterioration?
SELECT ONE ANSWER
i. Hypoglycaemia
ii. Fulminant lactic acidosis
iii. Severe hypocarbia
iv. Septic shock
v. Pulmonary hypertension
b. What further steps should be taken to manage her?
SELECT TWO ANSWERS
i. Intubation and ventilation to help correct acidosis
ii. i.v. sodium benzoate
iii. 20 ml/kg bolus of 10% dextrose
iv. Total parenteral nutrition
v. i.v. sodium bicarbonate to correct acidosis
vi. Bolus of 50% dextrose
vii. Broad-spectrum antibiotics
329
TO CASE 8.14
a. ii. Fulminant lactic acidosis
b. V. i.v.sodium bicarbonate to correct acidosis
,0 vii. Broad-spectrum antibiotics
C
("I)
� This child has developed fulminant lactic acidosis, secondary to acute metabolic decom
a· pensation of an underlying metabolic disorder. Management involves high-dependency
::,
V'l
0)
care, and liaison with a specialist metabolic unit for advice on further investigations
::, and n1anagen1ent.
0.
)> The metabolic acidosis should be corrected by an infusion of i.v. sodium
::,
V'l bicarbonate.
�
<D
'""I
V'l
Fluids should be 5% dextrose (there is no need for a bolus here and 10% dextrose is
- used as a bolus for hypoglycaemia). Protein should be excluded from the fluids since
0
'""I it would increase the metabolic acidosis. Broad-spectrum antibiotics should be given
,-+
:::J" to cover the possibility of infection.
<D
z Metabolic disease should always be considered in unusual presentations. The main
<D
� pointers towards a metabolic disorder are severe metabolic acidosis, lactic acidosis,
"TI hypoglycaemia, a raised anm1onia level and episodes precipitated by an intercurrent
0
3
Q.)
infection. It is unlikely to be a urea cycle disorder as blood ammonia was only slightly
raised, the lactic acidosis was severe and the child was not shmving any neurological
,-+
m
syn1ptoms.
><
Q.) Organic acidaemias can present with raised blood ammonia and severe metabolic aci
3 dosis because of accumulation of organic acids in body fluids, but in this child, blood
ammonia was only slightly raised. There appears to be a defect in intermediary carbo
hydrate metabolism associated with lactic acidosis. Indeed, this child was found to have
fructose-1,6-diphosphate deficiency, which was confirmed on white cells enzyme
studies. Fructose-1,6-diphosphate enzyme is one of the enzymes in the pathway of
gluconeogenesis, and is also needed for the conversion of fructose to glucose. Symptoms
may be precipitated by starvation, intake of fructose or sucrose and intercurrent
illnesses.
330
A female infant was born at 26 weeks' gestation by spontaneous vertex delivery. Her
mother was para 2 + 0 and previously well; she had received i.m. betamethasone 4 h
prior to delivery. The baby received two doses of surfactant within 12 h of birth, and
s:
;;,;:,
(')
completed 48 h of antibiotics which were stopped when the blood cultures and surface -0
(')
swabs, taken shortly after birth, were negative for infection. She is now 8 days old, has I
been ventilated since birth and is, at present, on half-enteral and half-parenteral -0
OJ
feeding. ;::i.
N
Her present ventilator settings are peak inspiratory pressure of 20 cm of water, end
expiratory pressure of 4 cm of water, inspiratory time of 0.42 s and inspired oxygen
concentration of 40%. The ventilator is set to patient-triggered ventilation mode.
You are called when there has been a sudden deterioration in oxygen saturations and a
drop in the heart rate.
On examination her oxygen saturation is 54%, heart rate 74 bpm and capillary refill
time <2 s measured over the sternum. There is poor chest movement with poor air
entry bilaterally. Her heart sounds are normal and there is no murmur.
What are the most likely causes?
i. Blocked endotracheal tube
ii. Tension pneumothorax
iii. Air trapping
1v. Pulmonary hypertension with right to left shunting
v. Duct-dependent congenital heart disease
1. Pneumonia
vi. Pulmonary haemorrhage
vii. Ventilator failure
331
i. Blocked endotracheal tube
ii. Tension pneumothorax,
t) viii. Ventilator failure
c;
ro
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o·
:::,
Any acute deterioration in a baby on a ventilator must raise the possibility of a mechani
cal failure, either with the ventilator itself, which should be checked thoroughly, or
V)
Q.)
by a blocked or dislodged endotracheal tube, which would show reduced chest move
:::, ment, or a pneumothorax. Other causes of acute deterioration, e.g. intraventricular
a.
haen1orrhage or sepsis, would not result in poor chest movement as a ne,v finding.
)>
:::, Pulmonary haemorrhage is usually accompanied by fresh blood from the endotracheal
tube.
""'I
V) Examination with a cold light source would diagnose a pneun1othorax, which can
-+,
0
""'I
occur as a complication in any ventilated baby.
r+
::::; Immediate m.anagement in this case involves checking the tube position by auscultation
(I)
over stomach as well as lung fields, suctioning of tube and changing the tube if it is
z
(I) blocked or dislodged, and decompression of a pneumothorax, if detected, by needle
thoracocentesis in the second intercostal space. A definitive chest drain can then be
-r,
0 inserted electively once the baby has been stabilised.
3
Q.)
r+
m
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Q.)
3
332
Fig 8.16
A previously well, term baby suffers a cardiac arrest on the postnatal ward on day 2 of
life. Resuscitation efforts are successful.
a. What does her ECG show?
i. P1 degree heart block
ii. P mitrale
iii. Long QT interval
iv. P wave occurring during repolarization phase
v. Atrial flutter
vi. Tachycardia
b. With what are these findings associated?
i. 22q11 deletion
ii. Tricyclic antidepressants
iii. Hypertrophic obstructive cardiomyopathy
iv. Clindamycin
v. Jervell-Lange-Nielson syndrome
333
TO CASE 8.16
a. iii. Long QT interval
iv. P wave occurring during repolarization phase
.0 b. ii. Tricyclic antidepressants
C
rt)
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o· The ECG shows a long QT interval. The QT interval varies with heart rate, and thus
,-+
::, the corrected QT interval (QTc) is calculated:

Vl
OJ QT interval
::, QTc =
0.. ✓if-R' interval
)>
::,
Vl where QT= time (s) from beginning of Q wave to end of T wave. Normal value of
QTc is <0.45 s.
--.
VI
-1-, Congenital long QT has two main variants: Romano-Ward, which is the more
0
--. common type, and the Jervell-Lange-Nielson forn1, which may be due to a recessive
,-+
:::; gene and is associated with deafness.
(I)
z
(I)
The drug cisapride has been associated with prolonged QT interval, as have various
other medications including some antibiotics and antifungals (e.g. erythrornycin and
.,,
0
fluconazole), terfenadine and tricyclic antidepressants .
3 Long-term oral beta-blockers decrease the risk of arrhythmias. Effectiveness is debatable,
OJ
,-+ but in infants the incidence of arrhythmia in the first year of life is decreased from
m 50% to less than 10%.
><
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3 Implantable defibrillators are effective but size limits their use to patients over 2
years old.
334
A 6-week-old girl is referred for investigation of prolonged jaundice and failure to
thrive. On examination she is also noted to have a heart murmur in the pulmonary area
and 3 cm hepatomegaly. Blood results show conjugated bilirubinaemia. Interestingly,
her 5-year-old sister is noted to be short, has been requiring extra help in school and
also has a heart murmur.
a. What would be the main investigations for the 6-week-old?
i. Stool for reducing substances
iii. Echocardiography
iv. Liver isotope scan
v. Direct Coombs' test
b. What is the likely diagnosis?
i. Biliary atresia
iii. Gilbert's syndrome
iv. a1-antitrypsin deficiency
v. Congenital hypothyroidism
c. What is the inheritance of this condition?
i. X-linked dominant
ii. Autosomal dominant
iii. Autosomal recessive
iv. X-linked recessive
v. Sporadic
335
a. iii. Echocardiography
iv. Liver isotope scan
b. ii. Alagille syndrome
c. ii. Autosomal dominant
The baby should have a liver isotope excretion scan plus liver biopsy to exclude biliary
0)
atresia as this would require prompt operative management.
:J
a.. These sisters have Alagille syndrome (arteriohepatic dysplasia). Patients with this syn
)> drome typically have chronic cholestasis, characteristic facies with a small pointed chin,
:J
VI vertebral arch defects, peripheral pulmonary artery hypoplasia or stenosis or other
congenital heart disease, failure to thrive and mild to moderate learning difficulties.
�
11)
VI
-+, Inheritance is autosomal dominant with variable expression. In this family the older
0
� sister had minimal liver involvement.
,-+
:::;
11) Ophthalmology examination to look for anterior chan1ber abnormalities (posterior
z
11)
embryotoxon), X-rays to look for abnormal vertebrae and blood for hypercholestero
� laen1ia can help confinn the diagnosis.
"TI
0
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3
336
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N
Fig 8.18
A 9-year-old boy presented to the A&E department at 02.00 h, with severe neck pain,
vomiting and drowsiness. He was well on going to bed. There was a history of
headaches over the last few months but no other relevant history. On examination,
GCS was 13, there was neck stiffness but no rash or fever. There were no focal
neurological signs. The fundi could not be visualised clearly. There were no other
physical signs. The cranial CT scans are illustrated.
What does the cranial CT scan show?
i. Mass lesion in foramen magnum
ii. lntraventricular blood
iii. Subarachnoid haemorrhage
iv. Space-occupying lesion right orbit
v. Normal sized ventricles
vi. Cerebral oedema
337
i. Mass lesion in foramen magnum
ii. lntraventricular blood
,0
C
(I)
The history suggests several possible differential diagnoses: spontaneous subarachnoid
haemorrhage, traumatic subdural or extradural haen10rrhage, acutely raised intracranial
Vl
o·
r+
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pressure or meningitis.
Vl
OJ Whatever the cause the initial managen1ent involves ABCD assessment. The conscious
:J
a. level and pupillary responses should be observed and assessed regularly. Blood glucose
)> should be checked in any patient with a decreased conscious level. This patient needs
:J
Vl an urgent CT scan, and neurosurgical and paediatric intensive care unit consultation is
�
(I) required early. In view of his reduced conscious level, he should not have a lumbar
"'"'I
Vl
puncture.
-
0
"'"'I The CT shows an extra-axial mass lesion in the anterior aspect of the foramen magnmn
r+
:J'" extending up to the pons, displacing and compressing the medulla posteriorly to the
left. There is intraventricular blood and early hydrocephalus. Both vertebral arteries are
(I)
z
(I) seen along with the mass lesion at the level of the foramen magnum. The lesion is
� likely to be an aneurysm arising from the vertebra-basilar junction projecting posteri
.,,
0 orly. This patient presented with a very acute history com_patible with intracranial
3 haen10rrhage. The headaches raised the possibility of a brain tumour or other space
OJ
r+ occupying lesion. Infection was much less likely. CT scan showed a brain stem vascular
m malformation vvith haemorrhage, and blood in the subarachnoid and intraventricular
><
OJ
spaces. Despite urgent neurosurgical referral, this patient deteriorated with further brain
3 stem bleeding and died.
338
A 7-year-old girl was referred to the endocrine clinic having developed axillary and
pubic hair over the last year. There was no breast development and she was
premenarchal. More recently, she had developed an adult body odour. On examination .s:
;::o
she looked well and was normotensive. She had some short dark hairs over her mons n
"'C
pubis but no cliteromegaly and longer darker hairs in her axillae (Tanner stage 2). n
:c
What is the differential diagnosis? "'C
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-,;
,-+
SELECT THREE ANSWERS ONLY N
i. Premature adrenarche
ii. Premature menarche
iii. Premature thelarche
v. Precocious puberty
vi. Constitutional precocious puberty
vii. Androgen-secreting tumour
339
i. Premature adrenarche
,0
C vii. Androgen-secreting tumour
(I)
V'I
o· The most likely diagnosis is prernature adrenarche, but congenital adrenal hyperplasia
r+
::::l (non-classical or simple virilising) and an androgen-secreting tumour of the adrenal

V'I
!l.J
glands or ovaries must be considered.
c..
::::l
Adrenarche (with the isolated appearance of pubic hair) is puberty of the adrenal gland
)> and is considered premature before the age of 8 years. It is characterised by greasy hair
:::i
V'I and skin, vveight gain, slight pubic hair development and an adult body odour. The
�
(I) bone age may be slightly advanced but adrenarche has no effect on final height. The
"""'I
VI
chief hormone produced is dehydroepiandrosterone sulphate (DHEAS); proposed aeti
-h
0
"""'I
ologies include a maturational increase in 17a-hydrm,rylase and 17,20-lyase enzymes
r+ and a reduction in 3�-hydroArysteroid dehydrogenase (3�-HSD). Although generally
:::;
(I) mild, the signs of adrenarche can be exaggerated and this can make it difficult to dis
z
(I)
tinguish clinically from congenital adrenal hyperplasia (CAH) or an androgen-secreting
� tumour. Cliteron1egaly often indicates a more serious cause of virilisation. CAH presen ts
-n with rapid growth and virilisation with cliteromegaly, most commonly due to 21CX
0
3
OJ
hydroArylase enzyme deficiency. Rather than presenting as a classical salt-wasting type,
the differential diagnosis in this case would be a simple virilising or late onset/nonclas
r+
m sical congenital adrenal hyperplasia. 11�-hydroArylase deficiency is rare, presenting with
X
OJ
virilisation and hypertension due to excess deoArycorticosterone levels. 3�-HSD defi
3 ciency is rare and presents with mild virilisation due to excess DHEAS levels.
Androgen-secreting trnnours often have a shorter history and clinical signs progress
rapidly. Girls with premature adrenarche n1ay be at increased risk of developing poly
cystic ovarian syndrome. Investigations include:
Biochemical investigations: basal androgens (testosterone, androstenedione, DHEAS),
basal 17-OHP and urine steroid profile
Radiological investigations: bone age and pelvic ultrasound scan
Further investigations: in cases where it is difficult to distinguish between adrenarche
and other causes of virilisation, one can consider a Synacthen test n1easuring cortisol
and 17-OHP (in non-classical 21-hydroArylase deficiency CAH, basal 17-OHP may
be normal but on Synacthen stirn.ulation, the 17-OHP will show an exaggerated
response) and a CT scan of the adrenal glands may be required if adrenal or ovarian
tumours are suspected.
340
A 3 h old baby, born at term in good condition after a normal pregnancy, was found
on the postnatal ward to be intermittently jerking. On examination, he was profoundly �
floppy and unrousable. His blood sugar was 4.2 mmol/1. Arterial blood gas: pH 7.03, ::0
(i
pCO2 9.5 kPa, pO2 5.1 kPa, HCO3 19 mmol/I and BE -3.2. He was transferred to the "'Cl
(i
neonatal unit and ventilated. Full septic and metabolic screens were performed. I
"'Cl
There was no hepatomegaly. CXR was unremarkable. U&Es, LFTs, calcium and OJ
magnesium levels were normal, as were blood lactic acid and ammonia levels. With �
N
ventilation, his respiratory acidosis corrected rapidly. An EEG showed burst suppression.
The baby continued to fit despite treatment with phenobarbitone. He lost all respiratory
drive, and became unresponsive to pain. Cultures of blood, urine and CSF were
negative. The metabolic screen revealed an elevated glycine level in the CSF, and an
increased CSF/plasma glycine ratio.
a. Suggest a diagnosis:
i. OTC deficiency
ii. Peroxisomal disorder
iii. Non-ketotic hyperglycinaemia
iv. MCAD deficiency
v. Urea cycle disorder
What therapies may be used in the treatment of this condition?
i. Carnitine
ii. Vitamin B12
iii. Benzodiazepines
iv. Forced alkaline diuresis
v. Dextromethorphan (NMDA receptor blocker)
vi. Sodium benzoate
343
TO 9.1
a. iii. Non-ketotic hyperglycinaemia
b. v. Dextromethorphan
vi. Sodium benzoate
This metabolic condition causes acute neurological distress, without hyperanunonaemia,
or n1etabolic acidosis, in the first hours of life. It is characterised by coma, hypotonia
OJ
and myoclonic jerks. The inheritance is autosomal recessive, with the metabolic lesion
::J being in the glycine cleavage syste1n, a corn_plex enzyme system with four enzyn1e
a.
components.
)>
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VI Other conditions such as sulphite oxidase deficiency and perioxisom.al disorders can
ro present in a similar way; however, they are associated with dysmorphism, and usually
'""I
VI present later. The diagnosis of NKH relies on the demonstration of elevated glycine
-h
0
'""I
in the CSF, and especially an elevated CSF/plasma glycine ratio. An EEG usually always
,-+ shows a burst suppression pattern.
::r
ro
Liaison with a neuro-metabolic specialist in a tertiary centre is essential. No consistent
z
ro effective treatment is known. High levels of glycine cause overstimulation of the N
methyl-D-aspartate (NMDA) receptors in the brain. Dextromethorphan, an NMDA
"TI
0 receptor blocker, has been used with variable success, as has sodium. benzoate, which
3
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conjugates glycine. L-carnitine, which promotes glycine conjugation with benzoate,
,-+ has also been tried.
m
>< Despite the above therapies, the prognosis is extrernely poor. Most infants die in the
OJ
3 neonatal period, and those that survive have severe mental retardation. Prenatal diag
nosis is now available for affected families.
344
s:
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ti
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ti
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a,
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N
Fig 9.2
A 5-month-old baby is referred by the GP who is concerned about the head shape. The
baby is thriving, there are no associated dysmorphic features, and the deformity is not
progressing.
i. Brachycephaly
ii. Scaphocephaly
iii. Hydrocephaly
iv. Plagiocephaly
b. What investigation is needed?
i. SXR
ii. CT head
iii. None
iv. Cranial ultrasound scan
345
TO CASE 9.2
a. iv. Plagiocephaly
b. iii. None
This abnormal head shape resembling a parallelogram is known as plagiocephaly. The
n1ost common cause of this condition is due to postural factors, which result from
external forces applied to the soft infant skull. Risk factors associated with plagiocephaly
include:
Restrictive intrauterine environment - such as large baby, multiple pregnancies, small
maternal pelvis, small or malformed uterus, etc.
)>
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II\
Prematurity - this makes the already malleable cranium even more susceptible to the
moulding forces
(1)
""'I
II\
Back sleeping - following the "Back to Sleep" campaign to reduce the risk of sudden
-h infant death syndrome, the number of infants presenting with plagiocephaly
0
""'I increased.
,-+
:,
(I) Detailed clinical examination is needed to rule out dysmorphic features associated with
z
(1)
craniosynostosis. If the deformity is severe and progressive, or if associated with other
� dysmorphic features, SXR and CT scan should be undertaken to exclude craniosyn
.,,
0
ostosis. Syndromes associated with craniosynostosis include Apert syndrome, Crouzon
3 syndrome and Pfeiffer syndrome.
OJ
,-+ Management of simple plagiocephaly involves a conservative approach with reassurance.
m The deformity becomes less obvious with age and scalp hair growth.
><
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3
346
A 10-year-old boy presented with a 24 h history of pyrexia, vomiting and tachypnoea.
His parents reported that, over the past month, he had been losing weight despite
eating well, and drinking more than usual. Otherwise he had been in very good health.
On examination, he was thin, more than 5% dehydrated, with a sighing respiratory
pattern.
Biochemistry: Na 148 mmol/I, K 4.1 mmol/I, urea 7 .8 mmol/I, creatinine 67 µmol/I and
bicarbonate 14 mmol/I.
a. Give three further initial relevant investigations:
i. Blood glucose
ii. Urinalysis
iii. FBC
iv. Bone marrow aspiration
v. CXR
vi. Echocardiogram
vii. Short synacthen test
viii. Blood gas
His condition improved with appropriate treatment, and he was discharged home 2
days later on regular medication. Two months later, he awoke with a moderate right
hemiparesis which resolved completely over the next 10 h.
b. What complication of his treatment is likely to have occurred?
i. Microembolic cerebrovascular accident
ii. Todd's paresis
iii. Fat embolus
iv. lntracerebral haemorrhage
v. Sagittal venous thrombosis
347
ANSWERS TO CASE 9.3
a. i. Blood glucose
ii. Urinalysis
viii. Blood gas
b. ii. Todd's paresis
This child initially presented in diabetic ketoacidosis. The history of weight loss, poly
OJ
dipsia, and polyuria in a previously well child is typical. Hypoglycaen1ia is a cornplica
:l tion of treatrnent, and in this case was significant enough to precipitate a seizure,
Q.
complicated by a Todd's palsy. Complete resolution of the neurological deficit is
)>
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348
A 5-day-old female infant was admitted following a cyanotic episode. No abnormal
movements were noted. On examination, she was active with oxygen saturation of 3;;,:
98% in air. She fed well on formula milk. She developed repeated apnoeic episodes in ;o
()
the hospital. A septic screen including lumbar puncture was undertaken and she was '"O
()
commenced on empirical antibiotic therapy. She subsequently had several apnoeic :c
episodes and required ventilation. '"O
a,
On day 2 of mechanical ventilation, she was on pressures of 14/3.5, a rate of 30/min
�
N
and 30% FiO2.
Blood gas analysis showed:
pH 7.42
pCO2 5.4 kPa
pO 2 8.1 kPa
BE 6.3
The results of other investigations:
Blood, urine and CSF cultures were negative
CXR was normal
ECG was normal
Serum ammonia and lactate levels were normal
On day 5, she was extubated and commenced on feeds. She again developed apnoeic
episodes.
i. Subclinical seizures
ii. Gastroesophageal reflux
iii. H-type trachea-oesophageal fistula
iv. Bulbar palsy with swallowing incoordination
v. Patent ductus arteriosus
b. What investigation is most useful to confirm this diagnosis?
i. EEG
ii. Prone oesophagram
iii. pH study
iv. Echocardiogram
v. Upper gastrointestinal contrast study
349
ANSWERS TO CASE 9.4
a. ii. Gastroesophageal reflux
b. iii. pH study
.0
C:
([)
Castro-oesophageal reflux is the most likely cause. In this case it was secondary to
� congenital hypertrophic pyloric stenosis. This condition occurs more frequently in male
o· infants. This infant had a family history of congenital pyloric stenosis.
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Investigations should include an oesophageal pH study and an upper GI contrast, and
Cl. a test to exclude pyloric stenosis if necessary.
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Fig 9.5
A 15-year-old boy was referred by his GP with possible pneumonia. He had a 2 week
history of cough and acute onset of chest pain made worse by deep breathing. There
was no history of vomiting, haemoptysis or injury. Past history was unremarkable and
he was on pizotifen for headaches. Initial examination revealed the following:
Temperature 37.7°C
Oxygen saturation 99% in air
Respiratory rate 22/min
Blood pressure 110/66 mm Hg
There was no chest wall tenderness, no wheeze or crackles, and the abdomen was soft
with no evidence of hepatosplenomegaly. An ECG (see Fig. 9.5) and CXR were carried
out.
The haematological and biochemical investigations were as follows:
Hb 18.6 g/dl
WBC 9.6 (neutrophils 6.4, lymphocytes 1.8)
platelets 376
•, ESR 31
r,(Rp 104
ALP 187
Albumin 41
Corrected Ca 2.44
An echocardiogram confirmed a small pericardia! effusion and normal ventricles. The
chest X-ray was reported by the radiologist as "marked widening of the mediastinum
suggestive of extensive mediastinal lymphadenopathy; the lungs appear clear".
What is your differential diagnosis?
i. Amyloidosis
ii. Tuberculosis
iii. Cardiomyopathy
iv. Glycogen storage disease
v. Sarcoidosois
vi. Leukaemia
vii. Mucopolysaccharidosis type IV
viii. Carcinoma of the bronchus
351
TO CASE 9.5
ii. Tuberculosis
v. Sarcoidosis
vi. Leukaemia
Differential diagnoses should include n1alignancy, lymphoma, leukaemia, tuberculosis,
and sarcoidoses.
OJ Further investigations needed are a repeat FBC and blood filrn, lactate dehydrogenase,
� a Mantoux test and a CT scan of chest and abdomen.
)>
:::s The ECG shov,rs low voltage in all leads suggestive of pericarditis. Bacterial infection
� accounts for 1-8% of cases and causes purulent pericarditis. These develop from direct
� pulmonary extension, haematogenous spread, myocardial abscess/endocarditis, penetrat
ing injury to chest wall from either traun1a or surgery, or a subdiaphragmatic suppura
tive lesion. Organisms isolated include Gram-positive species such as Streptococcus
,-+
::::r p11e111no11iae, other Streptococcus species and Staphylococcus, and Gram-negative species,
ro
including Proteus, E. coli, Pse11do111011as, Klebsiella, Salmo11ella, Sh(<l,ella, Neisseria 1neningi
z
ro tidis and Haenwphilus i1ifluenzae. Less common organisms include Legionella, Nocardia,
Actinobacillus, Rickettsia and Lyme borreliosis (Borrelia burgdo,jeri). Tuberculosis accounts
-n
0 for 4% of cases and viral infections account for 1-10% of cases. Causative viruses include
3
OJ
coxsackie B, echovirus, adenoviruses, influenza A and B viruses, enterovirus, murn.ps
,-+ virus, EBV, HIV, HSV1, varicella zoster virus, measles virus, parainfluenza 2 virus and
m respiratory syncytial virus. Other causes include renal failure, autoirnmune disease,
><
OJ rheurn.atic fever and ni.alignancy. The ECG is classically low voltage in all leads. Four
3 stages of ECG changes are described in acute pericarditis; hm}srever, n1any patients will
not exhibit all four stages.
The stages are as follows:
1. ST segrn.ent elevation and PR segrn.ent may be depressed.
2. ST segment is still elevated but returning to baseline with decreased T-wave
amplitude. PR segrn.ent is depressed.
3. ST segment returns to normal with T-wave inversion (rn.ay be incorn.plete in some
cases).
4. ECG normalisation occurs. T-wave changes may persist and do not necessarily
indicate active disease.
352
A 9-year-old girl presented to the outpatient clinic with a history of becoming
increasingly clumsy. She had been diagnosed as dyspraxic 2 years previously. $
:::0
Her parents described her as always having been clumsy. They noted her balance was n
-0
becoming worse over the previous 6-12 months. She was increasingly prone to falls n
:c
and found walking in a straight line very difficult. She could not manage zips or -0
buttons, and her writing was large, slow and difficult to read. OJ
;:i
Examination revealed a pleasant, co-operative 9 year old girl. She had a 1 cm x 2 cm N
cafe au lait patch on her left anterior chest wall. She had a mild thoracic scoliosis.
There was no pes cavus or clawing of her toes. General examination was otherwise
unremarkable. Neurological examination revealed normal cranial nerve function. There
was normal tone and power in the upper limbs, and reflexes were present, although
difficult to elicit. She displayed bilateral finger nose ataxia.
Lower-limb assessment revealed normal power with slight reduction in tone. Her knee
and ankle jerks were absent bilaterally. Plantars were extensor and she had reduced
proprioception. Her gait was ataxic with poor balance. Romberg's sign was positive.
i. Cerebellar syndrome
ii. Hereditary sensori-motor neuropathy
iii. Friedrich's ataxia
iv. Type II neurofibromatosis
v. Refsum's disease
vi. Kugelberg-Welander disease
353
ANSWER TO CASE 9.6
iii. Friedrich's ataxia
Early-onset ataxia sharing cerebellar and sensory ele1nents, areflexia and scoliosis is very
suggestive of Friedrich's ataxia, the n10st likely diagnosis in this case. Investigations
o· include MRI brain scan, spine X-ray, ECG/echocardiograrn, DNA for frataxin nmta
�·
:::, tion and nerve conduction studies.

Ill
OJ The onset of Friedrich's ataxia is between 2 and 16 years of age. It is autosomal reces
g_ sive with an incidence of approximately one in 50 000. The initial feature is ataxia or
)> clumsiness of gait in 95% of cases and scoliosis in 5%. Prognosis is poor with steady
:::,
Ill deterioration. Most patients are wheelchair dependent within 20 years of onset. All
�
ro tendon reflexes are absent in 75% of children. Ninety per cent of patients have extensor
""'I
Ill
plantar responses. Scoliosis develops in 80% of cases. Fifty-five percent of patients
-+,
0
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develop pes cavus, and 40% develop a cardiomyopathy. Treatment is supportive.
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354
A female infant was born by Caesarean section at 36 weeks' gestation after a
prolonged labour with failure to progress. Her mother was a previously well
primigravida. In the third trimester of pregnancy there had been polyhydramnios and
poor fetal movements. At birth she was floppy with very little respiratory effort. There
was a good initial response to bag ventilation but on withdrawal of support the heart
rate and oxygen saturation dropped.
On examination she was not moving, was hypotonic and had a poor suck. She also had
bilateral talipes. She needed a gradual increase in ventilation pressures over the first
24 h. The CXR revealed hypoplastic lungs.
i. Congenital hypothyroidism
ii. Werndig-Hoffman disease
iii. Congenital myotonic dystrophy
iv. Congenital myasthenia gravis
v. Prader-Willi syndrome
vi. SMA type I
vii. Congenital central hypoventilation syndrome
b. What investigation would you need to carry out to confirm your diagnosis?
i. Genetic studies
ii. Muscle biopsy
iii. Thyroid function tests
iv. Tensilon test
v. ECG
355
ANSWERS TO CASE 9.7
a. iii. Congenital myotonic dystrophy
b. i. Genetic studies
Congenital n1yotonic dystrophy (CMD) is the severest form of myotonic dystrophy
(MD). In CMD, inheritance (autosomal dominant) appears to be aln10st exclusively
from the mother. The diagnosis of n1yotonic dystrophy can be confinned by looking
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for gene defect in chromosome 19.
:;
Q. The severity of disease is related to the nun1ber of repeats within the abnorn1al gene.
)> Ventilation may be required for several weeks or even n1onths but there may be a
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VI general improve1nent in nmscle function after 3-4 months and if the neonatal period
�
ro is survived, then the child ·will progress in a similar way to classic MD. Complications
include n1.ental retardation, learning difficulties, cataracts, hearing problems, cardiac
-+.
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..., arrhythmias and chronic i::onstipation.
,-+
:::, Other myopathies could present in a similar way but CMD is by far the most common.
ro
A pregnancy with an affected fetus is often complicated by polyhydramnios, and labour
z
ro is likely to be prolonged because the mother is affected. Examination of the mother
�
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may aid the diagnosis - looking for myopathic facies and myotonia demonstrated by
inability to relax firm hand grip (e.g. following hand shake).
3
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356
Fig 9.8
An antenatal ultrasound scan at 22 weeks' gestation revealed a large lesion in the neck
of a female fetus. A postnatal T2-weighted MRI is shown.
a. In the antenatal period, which is the most important fetal investigation?
i. Nuchal thickness
ii. Karyotype
iii. Rhesus status
iv. a-fetoprotein
v. Fetal echocardiogram
b. What problem associated with this condition contributes to significant
mortality?
i. Congenital heart disease
ii. Hydronephrosis
iii. Pulmonary hypoplasia
iv. Hydrops fetalis
v. Haemolytic disease of the newborn
357
ANSWERS TO CASE
a. ii. Karyotype
b. iv. Hydrops fetalis
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(I) This MRI shO\;vs a cystic hygroma (cystic lymphangioma). These occur ,,1ith an inci
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dence of approximately 1/6000 pregnancies. On ultrasound and MRI, they appear as
complex multiloculated cystic masses, not infrequently having echogenic areas with
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haemorrhage. Nearly 80% of cystic hygromas involve the neck and frequently involve
:::i the floor of the 1nouth.
Q.
)> Antenatally, fetal karyotyping is necessary since about two-thirds of infants with an
:::i
antenatal diagnosis of cystic hygroma will have an abnormal karyotype: 42% have XO
(I) (Turner's syndrome) and 18% have trisomies (of chromoson1es 21, 18 and 13).
Cystic hygromas are associated with hydrops fetalis. Fetal death is a frequent outcome
if hydrops is present. If the pregnancy continues, obstructed or complicated labour and
,-+
::r delivery can occur. It is unusual for even very extensive lesions to inte1fere with
(I)
s,vallowing in utero, leading to polyhydramnios. Other structural lesions may coexist,
z
(I) particularly in infants with an abnormal karyotype.
-,, Very large masses such as this one may cause life-threatening airway compression. The
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immediate management is basic life support (ABC), first maintaining a stable patent
airway. With an abnormality this size one must liaise antenatally with senior ENT
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surgeons, paediatric surgeons and anaesthetists. They may be required at delivery to
X stabilise the patient's airway.
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3 Ex-utero intrapartum treatn1ent (EXIT) has been described, the basic principle being
the maintenance of intrapartun1 uteroplacental support while surgery is perforrned.
Definitive treatment consists of surgery. Con1plete excision is often not possible because
these lesions often infiltrate deep structures with little regard for tissue boundaries.
There is a high recurrence rate after excision. The other treatment option is the use
of sclerosants. In particular, OK-432 (a lyophylized n1Lxture of Streptococcus pyogenes)
has been used successfully in several published cases.
358
A 4-year-old girl had DTP, Hib and oral polio at 2, 3 and 4 months of age. She is
generally well, but had a febrile convulsion 10 days after her MMR at 18 months. Her
2-year-old brother is receiving chemotherapy for acute lymphoblastic leukaemia.
What immunisations, if any, should she not be given?
i. Diphtheria, tetanus and pertussis booster
ii. Meningococcal C vaccine
iii. MMR
iv. Inactivated oral polio
v. i.m. polio
vi. None
359
ANSWER TO CASE 9.9
i. Diphtheria, tetanus and pertussis booster
Diphtheria and tetanus booster, n1eningococcal C vaccine, MMR with advice regarding
temperature managernent, and inactivated polio (oral or intramuscular) in vie,v of her
immunocompromised sibling can all be given. Oral polio vaccine, which is a live
vaccine and n1ay be excreted in the stool, should not be given to inununosuppressed
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children, their siblings or other household contacts. Inactivated polio vaccine should
:::l be given instead.
Q..
)> A febrile convulsion is not a contraindication to further inmmnisations, but it is very
:::l
important to ,vatch the child closely for signs of fever. At the first observation of a
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Pertussis is not part of the pre-school booster schedule it should be just diphtheria
and tetanus.
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360
A 23-month-old girl had been restless and crying overnight, with a fever, cough and
hoarse voice. Next morning while awaiting a consultation with her family doctor, she
had a generalised seizure in the waiting room. She was given rectal diazepam, she
stopped fitting and was transferred by ambulance for evaluation in hospital. On arrival
she was "post-ictal ", had a temperature of 39.5° (, pulse rate of 90 bpm, respiratory
rate of 25/min, and SaO2 of 98% in room air. She was pale and hypotonic, with small
pupils. The triage nurse checked her blood glucose using a blood glucose meter. The
result was 0.9 mmol/1. A catheter urine sample was negative for standard dipstick
parameters except +ve ketones.
Give three possible underlying diagnoses
i. Organic acidurias
ii. Alcohol ingestion
iii. Beckwith-Wiedemann syndrome
iv. Febrile convulsion
v. Medium chain acyl CoA dehydrogenase deficiency
vi. Diabetic ketoacidosis
vii. Paracetamol overdose
361
TO CASE 9.10
i. Organic acidurias
ii. Alcohol ingestion
v. Medium chain acyl CoA dehydrogenase deficiency
After ABCs (airway, breathing, circulation), initial 1nanagement of this child involves
reversal of the hypoglycaemia. After gaining i.v. or intraosseous access, you need to
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administer a bolus of 10% dextrose followed by an infusion. If possible, take blood
::; samples for later analysis before injecting the dextrose (see below). Relatively conm1on
a.
causes of hypoglycaemia in this age group are ketotic hypoglycaemia and ingestion of
)>
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alcohol or oral hypoglycaemic agents. Rare causes vary from hormone insufficiency
(e.g. cortisol), liver disorders with hepatocellular failure, to a large range of inborn
.....
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errors of gluconeogenesis, fatty acid oxidation disorders, ketolytic defects and organic
- acidurias. A systen1atic approach is required to ensure that no possibilities are over
0
..... looked. Hypoglycaemia should be confirn1ed by formal laboratory analysis. Investiga
r-+
::; tions should include analysis for inborn errors (free fatty acids, plasma lactate, amino
(D
acids, -OH butyrate, cortisol and insulin).
z
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� This child was suffering from medium chain acyl CoA dehydrogenase (MCAD) defi
"Tl ciency. This autosonial recessive disorder of �-oxidation of fatty acids, generally presents
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clinically benveen the second rnonth and second year of life, often triggered by minor
illness. Hypoglycaemia occurs from an inability to oxidize fatty acids to ketones when
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glucose requirements cannot be met by gluconeogenesis. The combination of hypogly
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3 a major impact on brain function and underlies the mortality - up to 20% at initial
presentation. Initial laboratory examination of blood may reveal hypoglycaemia, mild
n1etabolic acidosis, hyperammonaemia and high uric acid levels. Liver function may
also be deranged. Examination of the urine often shows inappropriately low or absent
ketones. Biochemical testing of blood and urine for carnitine, acylcarnitines, acylgly
cines and organic acids is diagnostic for the disorder.
362
A 10-year-old Asian girl is referred with a 3 week history of polydipsia and nocturia.
There is no history of weight loss though she has been lethargic and not interested in
food over the last week. She was born by normal vaginal delivery at term and required
admission for a few days for monitoring her blood glucose as her mother had
gestational diabetes. She comes from a family of five; parents are non-consanguineous.
The mother was diagnosed as having gestational diabetes during her pregnancy with
our patient but since then has gone on to require insulin injections. The father has type
2 diabetes. The maternal grandparents died young, both had type 2 diabetes.
On examination her weight is > 99.6th centile and height is on the 98th centile. Her
blood glucose on testing was 12.1.
What is her most likely diagnosis?
SELECT ONE ANSWER ONY
i. Nephrogenic diabetes insipidus
ii. Juvenile type 1 diabetes
iii. Type 2 diabetes mellitus
iv. Insulin dependent diabetes mellitus
v. Cranial diabetes insipidus
363
ANSWER TO CASE 9.11
iii. Type 2 diabetes mellitus
D Features that might give a clue to the diagnosis include obesity, acanthosis nigricans,
C
(I)
and a family history of type 2 diabetes.
�
o· Conventional treat1nent of patients with type 2 diabetes usually begins with recon1-
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Vl n1endations for life style changes (i.e. diet and physical activity) often in parallel with
0,
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monotherapy with an oral agent such as metforrnin or gliclazide. If initial approaches
Q. fail, then a multidrug regimen, possibly including insulin, is prescribed. There may be
)> a role for glitazone treatn1ent in the paediatric age range, but this rern.ains to be clari
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Vl fied. However, with the increasing recognition of the progressive nature of the disease
(D and the high risk of micro- and macrovascular complications, it is recommended to
""'I
Vl treat it more aggressively to achieve glycaemic control.
-+,
Q Acanthosis nigricans is asymptomatic, brown-black, with a velvety texture. Peduncu

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::r lated skin tags are often present. The n1.ost common sites are the axillae, neck, and
(D
groin. Its presence is associated with insulin resistance.
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� Recently, the nurnber of type 2 cases has risen alarmingly in sorne parts of the world.
"Tl In the Southern United States, type 2 diabetes accounts for over 30% of new cases of
0
3
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diabetes in childhood. There is some evidence of a similar increase in numbers in the
UK. Most cases in the UK appear in the Asian subpopulation, although some Caucasian
r+
m children may also be affected. Type 2 diabetes is characterised by both insulin resistance
>< and deficient insulin secretion. Increasing obesity globally may be largely responsible
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3 for this increase. Treatment of these patients is complex because of the progressive
nature of the disease and the multifaceted physiological defects. It can take years for
subclinical hyperglycaemia to present as a symptomatic disease.
364
s:
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Fig 9.12.A
Fig 9.12.B
An 8-year-old boy who had been previously fit and well, was admitted with a rash and
a dry cough. For 2 days he had eaten very little, and on admission he was apyrexial but
sleepy. On examination, his respiratory rate was 30/min, with no recessions. He had
decreased air entry over the left chest with some basal crackles. He also had a fading
chickenpox rash over his trunk. A CXR was taken (see Fig. 9.12.A).
He improved over the next 24 h with i.v. antibiotics. It was noted that he had a history
of constipation as an infant. On further examination 72 h after his admission, a contrast
study was carried out (see Fig. 9.12.B).
What diagnosis does this contrast study confirm?
i. Left-sided hiatus hernia
ii. Left lower lobe pneumonia with pneumatocoeles
iii. Left-sided diaphragmatic hernia
iv. Congenital eventration of the diaphragm
v. Left-sided loculated empyema
vi. Left pulmonary hypoplasia
vii. Left-sided cystic adenomatoid malformation of the lung
365
ANSWER TO CASE 9.12
iii. Left-sided diaphragmatic hernia
Differential diagnoses from the X-ray alone include left lower lobe pneumonia, left
sided cystic congenital anomaly of the lung and a left-sided diaphragn1atic hernia.
A barium meal examination shmvs contrast in the left thoracic cavity in loops of small
bowel, confirming the diagnosis of diaphragmatic hernia.
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Late presentation of congenital diaphragmatic hernia is rare. It is important to recognise,
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as, with appropriate treatrn.ent, all such children have a normal life expectancy. At any
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congenital diaphrag1natic hernia.
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366
An 11-year-old girl presents with a 4-week history of abnormal movements and
difficulty walking. The school had noticed that her hand-writing had progressively
deteriorated and she has difficulties with daily activities such as dressing and using
cutlery. She has mild slurring of speech. The movements disappear during sleep. There
are no other symptoms of note and no recent history of fever, rash or upper respiratory
tract infection. Antenatal history and delivery were unremarkable. She has previously
been healthy, takes no medication and her siblings are well. There is no family history
of movement disorder or significant illness. On examination, she was alert, active and
afebrile. She was normotensive. General examination was unremarkable. There was no
organomegaly on abdominal examination. Fundoscopy showed normal appearances
and cranial nerve examination was normal. She had bilateral choreiform movements in
her hands on extension and pronation, and a positive "milkmaid sign". Choreiform
movements of the tongue were also seen on attempted protrusion. Bulk and power
were normal in all limbs but tone was slightly decreased.
i. Posterior fossa tumour
ii. Sydenham's chorea
iii. Huntington's disease
iv. Lesch-Nyhan syndrome
v. Parkinson's disease
vi. Pesticide poisoning
367
ANSWER TO CASE 9.13
ii. Sydenham's chorea
Sydenham's chorea is rare but the m.ost likely diagnosis in the absence of clinical fea
tures to suggest alternative conditions.
Investigations should include:
MRI brain, to exclude space-occupying lesion
a,
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throat swab
0.. ASO and anti-Dnase B titre to look for supportive evidence of streptococcal
)> infection
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ECG and echocardiogram to look for rheurnatic carditis
� antinuclear antibody and ESR to exclude connective tissue disease
�
thyroid function tests, PTH, U&E and bone profile should be checked, smce
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hyperthyroidism., hypoparathyroidism and Addison's disease can present with
r+ chorea
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(I) • LFTs, serurn copper and caeruloplasmin, amino acid screen, organic acid screen and
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lysosomal enzymes should also be checked
.,,
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This list is by no means exhaustive as the conditions associated with chorea are protean.
A toxicology screen should be considered in a child presenting acutely. Although there
3
a,
is no family history of Huntington's disease, DNA analysis for this disorder should be
r+ considered if other tests are inconclusive.
m
X
a, Haloperidol and diazepam may be used in the management of Sydenham's chorea.
3 Secondary prophylaxis with penicillin V should be given until adulthood.
Jones' criteria for diagnosis of acute rheumatic fever

Two major versus one 111.ajor and t\vo minor criteria with evidence of a recent strep
tococcal infection.
Major criteria
Carditis: 50% of patients with ARF and always associated with a murmur of
valvulitis
Polyarthritis: 70% of patients and manifested by a migratory arthritis of major
joints
Sydenham's chorea: 15% of patients and manifested by abnormal behaviour and/or
involuntary, purposeless movements
Erytherna rnarginatum: 10% of patients and is an evanescent, pink rash with ser
piginous borders
Subcutaneous nodules: 2-10% of patients and manifested by painless nodules over
extensor surfaces of large joints, the occiput, and/or vertebral processes
Minor criteria
Arthralgia: can only be considered in the absence of arthritis
Fever
Elevated acute phase reactants: ESR, C-reactive protein
Prolongation of the PR interval on ECG
Exceptions to the Jones' criteria include:
Sydenharn. chorea alone or indolent carditis alone (each of which may appear late,
and therefore, may not be associated with supporting evidence of a recent strep
tococcal pharyngitis)
Patients with a previous diagnosis of ARF who have a recurrence ni.ay not fulfil
the Jones' criteria due to the subtle presentation
368
A 5-day-old baby was admitted with a persistent fever and jaundice. He was also
reported to be snuffly and drowsy. Examination showed a jaundiced, sleepy baby with a s::
temperature of 38°C. His heart rate was 126 with a respiratory rate of 64. There were ;o
(')
no other positive findings. Initial investigations showed: "tJ
(')
Hb 15.3 g/dl :c
wee 5.o x 109/I "tJ
Platelets 119 x 109/I """
a,
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Na 136 mmol/I N
K 4.0 mmol/I
Glucose 5.4 mmol/I
CRP 64 mg/I
AST 636 IU/I.
A CXR was unremarkable and lumbar puncture showed WBC 3/mm3, RBC 35/mm3,
protein 0.84 g/I and glucose 2.6 mmol/1.
Over the next 24 h he became more unwell with poor perfusion and marked respiratory
distress eventually requiring ventilatory support. In the same period he also had an
episode of right-sided twitching lasting 30 s. Repeat examination revealed an enlarged
liver and further investigations showed deranged clotting and an AST of 1399 IU/1.
a. What medication would you have added in when the baby deteriorated?
i. Steroids
ii. Mannitol
iii. Acyclovir
iv. Nitric oxide
b. What non-haematological investigation would be most useful in initially
confirming the diagnosis?
i. Urine for virus particles
ii. CT scan
iii. EEG
iv. Skin swabs for virology
369
9.14
a. iii. Acyclovir
b. iii. EEG
Neonatal sepsis should be the initial diagnosis at presentation, and should be managed
with resuscitation, an infection screen and initiation of appropriate antibiotics and
ongoing supportive care. The n1.ost likely organism implicated in this age group is
Group B streptococcus.
The diagnosis of suspected HSV infection is suggested by the age at presentation, the
deranged clotting and massively elevated AST and the presence of seizures. The baby
was subsequently proven to have disseminated HSV infection. It is important to note,
as in this case, that there may be no maternal history of herpes infection.
An EEG would help in making the diagnosis, which characteristically shows
temporo-parietal high-voltage, low-frequency activity in the presence of HSV
meningoencephalitis.
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370
A 6-month-old girl was being investigated for failure to thrive and passing loose, fatty,
bulky stools. On examination she was found to be small (weight <3 rd centile, birth
weight 50 th centile) and had a florid eczematous rash. Her sweat chloride was normal,
and FBC showed a mild pancytopenia including an absolute neutropenia. A bone
marrow aspirate was therefore undertaken.
i. Acute lymphoblastic leukaemia
ii. Wiskott-Aldrich syndrome
iii. Schwachmann's syndrome
iv. Cystic fibrosis
v. Diamond-Blackfan syndrome
b. What complications is she at risk of developing?
ii. Sepsis
iii. Malignancy
iv. Hypertension
v. Allergic bronchopulmonary aspergillosis
vi. Cirrhosis of the liver
371
a. iii. Schwachmann's syndrome
b. ii. Sepsis
iii. Malignancy
Schwachmann's syndron1e is an autosomal recessive condition, and is the second rnost
con1mon cause of exocrine pancreatic insufficiency in the UK after CF.
0,
::,
The diagnosis is generally made after a con1bination of neutropenia (can be cyclical),
0.. thrombocytopenia and pancreatic insufficiency is found. Bone marrow aspirate and liver
)> biopsy can aid diagnosis.
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Complications include severe sepsis secondary to neutropenia, requiring inpatient treat
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rnent with broad-spectrum antibiotics, skeletal abnorn1alities secondary to metaphyseal
--+, dysplasia, and there is a srnall risk of leukaemic transformation, thus annual surveillance
0
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Fig 9.16
A 6-year-old girl presented a year ago with pallor (Hb 6.2 g/dl, MCV 69) and was found
to be iron deficient. Five months later, she re-presented with intermittent cough
productive of a small amount of blood. She had no history of fever. She was not
breathless on exertion. On examination, she was mildly clubbed. On auscultation of her
chest, there were bilateral basal crackles.
Investigations showed:
Clotting normal
U&E normal
LFT normal
Urinalysis - no blood or glucose; trace of protein
Faecal occult blood positive.
Her CXR and CT scan are shown (Fig. 9.16.a, b)
i. Pulmonary haemosiderosis
ii. Sickle cell disease
iii. CF
iv. TB
b. Select one other investigation to help confirm the diagnosis:
i. Bronchoalveolar lavage microscopy
ii. Pulmonary function tests
iii. Sweat test
iv. Mantoux test
373
ANSWERS TO 9.16
a. i. Pulmonary haemosiderosis
b. i. Bronchoalveolar lavage microscopy
Pulmonary haemosiderosis is characterised by recurrent episodes of intra-alveolar haem
orrhages, production of blood-stained sputum containing haemosiderin-laden macro
phages and acute anaemia.
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Sputum or bronchoalveolar lavage microscopy can be used to confirm the diagnosis;
0.. showing haemosiderin-laden macrophages. An open lung biopsy can also be performed;
)> showing intra-alveolar haemorrhages and haemosiderin-laden n1acrophages within
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VI Aetiology
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1. Prin1ary: idiopathic
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11. Goodpasture's syndrome
111. heart disease, e.g. mitral stenosis
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1v. collagen vascular disease, e.g. polyarteritis, rheumatoid arthritis
3 Maintenance treatment includes inhaled steroids or low-dose, alternate-day, oral ster
Q,)
,-+ oids. Azathioprine has been used. Son1e patients are able to discontinue treatment
m benveen acute episodes. Oral iron is given to correct anaemia.
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3 The clinical course waxes and wanes in severity. Microscopic hae1norrhages lead
to chronic anaen1ia. Treatrnent of acute episodes consists of blood transfusion and
i.v. hydrocortisone. Long-term prognosis is variable. Acute n1assive haen10rrhages can
be fatal.
374
An 8-month-old boy was admitted with a 4 hour history of breathing difficulty. On
examination, he was apyrexial, he had a barking cough, inspiratory stridor and a
respiratory rate of 35/min. He was treated with oral steroids. Over the next 48 h his
s:
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condition fluctuated with periods of marked stridor and respiratory distress at night but
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improvement during the daytime. His condition worsened dramatically 72 h after
.,,
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admission; he appeared grey and sweaty with a high pyrexia, tachycardia and severe OJ
respiratory distress with oxygen saturations in the mid-80s. .....
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What is the cause of his deterioration?
i. Epiglottitis
ii. Septicaemic shock secondary to foreign body
iii. Bacterial tracheitis
iv. Hypocalcaemia
v. Anigoneurotic oedema
375
iii. Bacterial tracheitis
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The initial history here suggests viral laryngotracheobronchitis, i.e. croup. Bacterial
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tracheitis 1nay occur as a seconda1y infection, usually in children less than 3 years old.
:Ar··· Causative organisms include Staphylococcus aureus, Haemophilus injluenzae and Streptococcus
e
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pne11moniae.
Q) Management includes intubation and ventilation, frequent suctioning of the airway and
a.
::::::s
appropriate antibiotics. At laryngoscopy mucosal swelling is seen at the level of the
)> cricoid with thick, purulent secretions.
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Complications include pneumonia, septicaemia, respiratory arrest, and subglottic

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stenosis.
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376
Fig 9.18
A 17-day-old baby was brought to the A&E department after his mother, who was
carrying him in a baby sling, accidentally tripped and fell over. He had slipped from his
baby sling on to the pavement hitting the front of his head, and had cried immediately.
On examination, two large parietal swellings were noted, and neurological assessment
was normal.
What do the SXR and CT scan show?
i. SXR - normal
ii. SXR - occipital fracture
iii. SXR - bilateral parietal fractures
iv. SXR - right temporal fracture
v. CT - normal
vi. CT - small right-sided subdural haemorrhage
vii. CT - cerebral oedema with slit-like ventricles and midline shift
viii. CT - small right-sided extradural haemorrhage
iii. SXR - bilateral parietal fractures
vi. CT - small right-sided subdural haemorrhage
The SXR (AP view) demonstrates large bilateral parietal fractures. Figure (b) shows a
lateral view of the skull, demonstrating fractures extending from the coronal sutures
anteriorly, to the lan1boidal sutures posteriorly. Figure (c) is a CT of the brain, showing
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a small right-sided subdural haemorrhage with no midline shift.
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a. Further assessment should take the forn1 of observation. In particular, the child's arousal
)> state, pupil size and reactivity, heart rate, and blood pressure should be monitored at
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VI least half-hourly for 24 h, in order to detect any deterioration. The Glasgow neurologi
(I) cal scale could not be applied directly in view of the child's age. Even scales specifically
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cal irrnnaturity. The subdural haemorrhage is small, so no surgical intervention is indi
,+ cated. Should the child deteriorate and develop signs of raised intracranial pressure
::,
(I) (drowsiness, vomiting, bradycardia and hypertension), a repeat CT scan is indicated to
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look for evidence of an extending lesion. The mother should be informed that the
� fractures will heal without intervention, and the subdural will gradually resolve. There
,,
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should be no long-term_ sequelae but the child will be followed up.
3 One should consider the possibility of non-accidental injury, and a general examination
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,+ should look at the general state of the child to ensure he is clean, thriving, and has
m not got any bruises of concern (although he will most certainly have bruises related to
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this injury). Ensure his frenulmn is intact and there are no retinal haemorrhages. A
:3 skeletal survey and an ophthalmological examination should be arranged. Social services
should be infom1ed and a strategy meeting held. Liaison should also take place with
the midwife and GP to ensure there are no concerns about this family.
378
1. Ostium secundum atrial septal defect 6. Patent ductus arteriosus
2. Ventricular septal defect 7. Pulmonary valve stenosis
3. Transposition of the great arteries 8. Coarctation of the aorta
4. Total anomalous pulmonary venous 9. Tetralogy of Fallot
drainage 10. Hypoplastic left heart syndrome
5. Atrioventricular septal defect
the list above:
a. An infant is seen for his 6-week check and found to have a loud ejection systolic
murmur in the third left intercostal space and a single second heart sound on
examination. There is no obvious cyanosis but a suggestion of mild desaturation. On
the CXR there is a concavity on the left heart border and decreased pulmonary
vascular markings.
b. An infant is found profoundly cyanosed and lethargic in his cot on day 2. On
auscultation there is a soft systolic murmur heard inconsistently at the left sternal
edge and a single second sound. The CXR shows a narrow upper mediastinum,
hypertrophied right ventricle and increased pulmonary vascular markings. The ECG
shows a normal neonatal pattern.
c. An 11-month-old girl presented to the local hospital with a 1 week history of
cough, wheeziness and increasing lethargy. She was given bronchodilators but failed
to respond. Her oxygen saturation on admission was only 70-80% despite 100%
oxygen. She was intubated and ventilated and nitric oxide was given but without
clinical improvement. On examination, she was cyanosed with a hyperactive
praecordium. Her chest revealed scattered wheezes and crackles. There was a
palpable liver of 2-3 cm. Her CXR showed a "cottage loaf" appearance.
379
9.19
a. 9. Tetralogy of Fallot
Fallot's tetralogy accounts for about 5% of congenital heart defects. The constituents
of Fallot's tetralogy are: obstruction to right ventricular outflow tract, VSD, over
riding aorta and right ventricular hypertrophy. Children n1ay be centrally pink in
early infancy, but cyanosis is usually present by the end of the first year. There 1nay
OJ
:J
be clubbing. Children have cyanotic "spells" due to decreased pulmonary blood
a. flow which can occur during crying or exertion. To alleviate these spells, children
)> may employ "squatting" which increases the systemic vascular resistance, reduces
:J
venous return from the legs and in1proves the puln10na1y blood flow. Complications
include cerebral thrombosis, cerebral abscess, bacterial endocarditis and a haem.or
·""'\
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rhagic tendency.
0
,-+ b. 3. Transposition of the great arteries (TGA)
::::;
(D TGA constitutes about 5% of all congenital heart diseases and is the most common
z cyanotic heart disease present in the imn1ediate postnatal period. It is slightly more
(D
conunon in males. In TGA, the normal serial circulation is changed to a parallel
'"T1 circulation resulting in complete separation of the systemic and pulmona1y circuits.
0
""'\ Hypoxaemic blood circulates in the body, whereas the hyperoxaemic blood circu
3 lates in the lungs. Defects such as a patent ductus arteriosus or atrial septal defect
OJ
,-+
m are crucial for mixing these two circuits and for survival. Because of this, infants
OJ usually present in the first few days of life when the PFO and PDA show signs of
3 closure. Once the diagnosis is made, a prostin infusion should be conunenced and
transfer to a paediatric cardiac unit should be arranged. Often a Rashkind balloon
septostomy is pe1formed in infants with a small or closing atrial communication in
order to improve mixing.
c. 4. Total anomalous pulmonary venous drainage (TAPVD)

In TAPVD, the pulmona1y veins (PV) drain into the right atrium (RA) rather than
into the left (LA). An atrial conmrnnication is essential for survival. TAPVD
accounts for 1 % of all congenital heart diseases and there is a marked male prepon
derance (4: 1) in the infracardiac type. Four types are distinguished
Supracardiac: (50%) the common PV drains into the SVC via a vertical vein and the
left innominate vein
Cardiac: (20%) the co111111on PV drains into the corona1y sinus or the PVs drain into
the RA through four separate openings
Infracardiac: (20%) the common PV drains into the portal vein, ductus venosus,
hepatic vein or the IVC
lVIixed type: 10%: a combination of the other types
In the absence of PV obstruction, the child presents with mild cyanosis, growth
retardation and heart failure; whereas in the case of PV obstruction, the presenta
tion is with severe cyanosis and respiratory distress in the neonatal period. The
CXR showing the "snowman" or "cottage loaf" appearance is typical of
supracardiac TAPVD. This appearance is usually only visible after 4 months of
age.
r
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n
I
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N
Fig 10.1.A Fig 10.1.B
A12-year-old boy presented with a 3-year history of anxiety, school phobia and lack of
energy during which he had gained excessive weight, despite a normal diet. Prior to
this he had been fit and well with a normal birth history and no developmental
concerns. His weight was 66.7 kg (above the 97 th centile) and height 144.9 cm (25 th
centile). On examination he was obviously overweight, had coarse facies, very dry skin
and absent ankle jerks (Fig. 10.1.A). There was a small palpable goitre and his pulse
rate was 60 bpm. A bone age was delayed at 8.7 years. He was started on treatment
and there was significant improvement in his symptoms and physical appearance
(Fig. 10.1.B).
What is your clinical diagnosis?
i. Hypopituitarism
ii. Craniopharyngioma
iii. Cushing's syndrome
iv. Congenital hypothyroidism
v. Acquired hypothyroidism
vi. Euthyroidism
383
v. Acquired hypothyroidism
The clinical diagnosis here is acquired hypothyroidism, which is most likely to be of
autoin1mune origin and also known as chronic lyn1phocytic thyroiditis. Both goitrous
(Hashimoto's) and non-goitrous (prirnary myxoeden1a) fom1s are described. In about
30-40% of cases, there is often a strong :fan1ily history of autoi1runune thyroid disease.
a,
Presentation may be at any age but is more c01runon during adolescence and is more
:::J com1T1on in females.
0.
)> Investigations should include thyroxine, TSH and thyroid antibodies. Elevated TSH
:::J
VI den1onstrates primary hypothyroidism. If thyroxine levels are normal in the presence
�
(I) of raised TSH, then it is described as compensated hypothyroidism, but may progress
"""I
VI
to overt hypothyroidism (low thyroxine levels). Antibodies to thyroglobulin and thyroid
-
0
"""I
peroxidase (TPO) are detectable in 95% of cases. TPO antibodies are more sensitive
,-+ and specific. Bone age is delayed. This patient had a TSH of >150 mU/1 (norrnal
::;
(I) <6 mU/1) and a thyroxine level below 20 nmol/1 (norn1al 70-140 nmol/1).
z
(I) Treatment should be conm1enced with L-Thyroxine at a dose of 100 mcg/nl. Dosage
�
.,,
0
will need to be adjusted according to symptoms and biochemical testing. Follow-up
to monitor growth and puberty is essential.
3
a,
,-+
m
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384
A 7-year-old Somali boy was referred to the paediatric surgical team for drainage of a
large abscess on his left buttock. A history was difficult to obtain as the family had
recently come to the UK from Somalia, but, with the help of an interpreter, it transpired
that the boy was prone to recurrent abscesses in various sites of his body. On three
previous occasions, he had had to be admitted to hospital for surgical drainage of the
abscess. Following the abscess's successful drainage, the child was treated with a 5-day
course of i.v. flucloxacillin (as pus from the abscess revealed a growth of Staphylococcus
aureus), and the boy was discharged home, to be reviewed by the paediatric medical
team in the out-patient clinic in 4 weeks' time.
What diagnosis is the history suggestive of?
i. Defect in cellular immunity
ii. T-cell deficiency
iii. SC::ID
iv. Agammaglobulinaemia
v. Neutrophil disorder
vi. lgA deficiency
vii. Phagocytic disorder
38'5
TO 10.2
v. Neutrophil disorder
vii. Phagocytic disorder
In suspected inunune deficiency, a full history is important, especially of gingivitis,
mouth ulcers and fever, and any family history of recurrent serious infections suggestive
of immune disorder. Exarn.ination should include height and weight, and evidence of
DJ
failure to thrive. Knowing when and how to investigate is important. Until 5 years of
::J age, normal children have up to 12 respiratory infections per year. Frequency is influ
0..
enced by: presence of older siblings, child-care attendance and exposure to tobacco
)>
::J sn1.oke. The child is likely normal but prone to infections if infections are mild, acute
and probably viral; recovery is usually without sequelae; growth pattern is normal;
....
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infections are restricted to a single site suggest local obstruction, i.e. an anatomical
-n problem. This history is highly suggestive of a neutrophil problem. Investigations should
0
.... be in two stages. A large number of inu1mne function tests are available. It is therefore,
,-+
::;- important to choose the most appropriate. After a detailed history and a careful clinical
ro
examination, an idea should be gained of which immunity is involved:
z
ro 1. Cellular immunity:
.,,
0
a. Cells involved: T-lymphocytes and CD4 and CDS cells; T-cell help is required
for B-cells to function normally
3OJ b. Clinical picture: pneumocystis carinii pneumonia, persistent oral candidiasis,
rt persistent diarrhoea (rotavirus or other viruses), failure to thrive, for example
m
><
severe combined immunodeficiency disease or HIV
OJ 2. Humoral inununity:
3 a. Cells involved: B-cells from the bone marrow; these produce antibodies but
need help from T-cells
b. Clinical picture: sino-pulmonary infections (otitis media, sinusitis, etc.), espe
cially with encapsulated bacteria, and serious infections such as osteomyelitis,
septic arthritis and meningitis
3. Complement system:
a. A series of proteins that interact sequentially on the cell surface in a cascade,
starting with either the classical or alternative pathway and leading to a conunon
pathway that generates chemotactic factors and opsonins, and causes cell lysis
b. Clinical picture: recurrent bacteraemia and meningitis (especially neisserial
infections)
4. Phagocytic system:
a. Cells involved: neutrophils
b. Clinical picture: boils, furunculosis, mouth ulcers, gingivitis and deep-seated
abscesses. There is increased susceptibility to Staph aureus, Gram-negative
bacilli, such as Pseudomonas and fungi, for example Aspergillus
5. Natural killer cell function:
a. Cells involved: natural killer cells kill virus-infected cells, some microorganisms
and tumour cells spontaneously, being stimulated by intetferon
b. Clinical picture: this is important in recovery from herpes infection (HSV,
CMV and herpes zoster virus), especially when haemophagocytosis is
suspected
386.
Table 10.2.
Investigations How performed Interpretation
First line s:
;:;tJ
Neutrophil count Blood film Congenital and acquired ()
neutropaenia '"tJ
()
Serum lgE Nephelometry or ELISA Very high in hyper-lgE syndrome I
---�-"- ~-�-�---- '"tJ
OJ
Second line �
NBT (nitroblue tetrazolium test) Specialised laboratory Chronic granulomatous disease N
Neutrophil function tests, e.g. Specialised laboratory If NBT is -ve and neutrophil defect
chemotaxis, is suspected
chemoluminescence
Weekly neutrophil count for Blood film Suspected cyclical neutropaenia
6/52 (fever± infection ± mouth ulcers
every.3 weeks)
CD11, CD18 Fluorescent-activated cell sorter Suspected leukocyte
(FACS) adhesion defect (delayed
separation of umbilical cord,
severe early infection)
386A
A 10-year-old is brought to A&E by his grandparents with complaints of sudden high
fever, lethargy and drowsiness. While being assessed, he has a prolonged generalised s::
seizure. He remains unconscious despite cessation of the seizure with diazepam. He is :::0
{')
admitted with a diagnosis of probable meningoencephalitis. Nursing staff discover that -0
{')
he attends a boarding school. His parents work along the East African coast as :r:
missionaries and he has recently spent the Christmas holidays with them. -0
QI
What further investigations are essential for this child as a guide for immediate �
N
action?
i. CXR
ii. Thick and thin blood films
iii. FBC
iv. Ammonia
v. Blood glucose
vi. Calcium
vii. Stool for ova, cysts and parasites
viii. Stool for M,C& S
CASE 10.3
ii. Thick and thin blood films
iii. FBC
v. Blood glucose
Foren10st, hypoglycaemia nrnst be looked for and treated appropriately. Other initial
laboratory tests should include FBC, U&E, blood gas analysis, a blood culture and
repeated blood films for malaria parasites. A lumbar puncture should only be pe1formed
if there are no clinical indicators of raised intracranial pressure.
The blood film. in this case was reported as "scanty :falciparum malaria parasites seen".
This suggests a diagnosis of cerebral malaria. Although a heavy parasitaemia is associated
with an increased risk of severe anaemia, a scanty parasitaernia may follow tissue seques
tration of mature parasites or partial treatment. Parasites in the blood film, however,
do not rule out meningitis or encephalitis. A !urn.bar puncture for CSF analysis is always
,-+ mandatory.
:::;
(I)
The convulsion and subsequent coma could be due to hypoglycaemia, deranged meta
z
(I) bolic status, particularly severe acidosis or the disease process itself Hypoglycaemia is
,,
0
a poor prognostic marker in severe malaria.
3
CJ
The definitive treatment is an antirn.alarial drug. The correct drug, dosage and route
are irn.portant. The decision of which drug to use is best guided by national policy
,-+
m which considers known local drug sensitivities. Quinine (i.v.) remains the drug of
>< choice for the treatment of cerebral n1alaria, although novel drugs are available includ
cu
3 ing the artemesinin derivatives. In addition, broad-spectrum antibiotics for possible
meningitis and septicaemia must be cornrn.enced until definitive diagnosis is niade.
Control of intractable seizures may be difficult. Phenytoin is often effective. Anti
pyretics are used for control of fever.
Supportive treat1nent is of paramount irn.portance. Blood glucose, parasite clearance,
haen10globin, renal function, and conscious level must be monitored.
Transfusion is only indicated if symptorn.atic, othenvise the anaern.ia will often correct
spontaneously. Thrmnbocytopaenia is con1mon in :falciparum infection but is not linked
to a poor prognosis and recovers spontaneously, so that, unless there is a bleeding dia
thesis, platelet transfusion is rarely necessary.
At follmv-up, these patients require careful examination for neurological sequelae,
including hemiparesis, blindness, cerebellar defects and seizures.
388
1. Asthma 6. VSD
2. Bronchiectasis 7. Gastroesophageal reflux
3. TB 8. ASD
4. CF 9. Bronchiolitis obliterans
5. Pneumocystis carinii 10. Mitra! stenosis
the list above:
a. A 3-year-old boy presents with worsening cough and breathlessness of 3 weeks'
duration. He has always been prone to infections. When he was 2 years old he had
chicken pox for 4 weeks. On examination, he has an emaciated appearance, his
weight is below the 0.4th centile, he has a temperature of 37.6° ( and he has
generalised crepitations on auscultation of his chest. A blood count shows severe
lymphopenia.
b. A 14 years old Malaysian boy living in a small village presented at a local clinic with
a history of increased breathlessness over the past few weeks. He has a history of
previous illness and was admitted to hospital for 2 weeks when he was 8 years old.
On examination the apex beat is located in the 5 th left intercostal space, mid
clavicular line and there is an audible murmur.
c. A 6-week-old girl had an uncomplicated birth at term following a normal pregnancy.
At 6 weeks' of age she was admitted with a cough, fever, increased breathlessness
and an increased oxygen requirement. She vomited, became breathless and
deteriorated 48 h after admission. On examination she was not dysmorphic. Heart
sounds were normal. Her respiratory rate was 60 bpm and she was recessing. There
was biphasic wheeze heard throughout her lung fields. Her oxygen saturations were
90% in air. A CXR showed consolidation of the right middle lobe. She was
commenced on low flow oxygen, intravenous fluids and broad-spectrum antibiotics
after appropriate cultures were taken. She responded well and feeds were
recommenced after 48 h. After a further 48 hours she relapsed and required
intubation and ventilation again.
389
10.4
a. 5. Pneumocystis carinii
Pneumocystis carinii causes a diffi1se pneumonitis with fever, tachypnoea, hypoxaemia
and bilateral diffuse infiltrates on X-ray. It often leads to respiratory failure and the
need for intubation and ventilation. Pneumocystis carinii pneumonia (PCP) occurs
almost exclusively in the imnmnocompromised host. Children with congenital or
acquired immune deficiency syndrome (AIDS), and recipients of suppressive therapy
in the treatment of malignancies or after organ transplantation are at high risk.
PCP is an AIDS-defining illness. It is the most common opportunistic life-threatening
lung infection in infants with perinatally acquired HIV disease. PCP in the HIV patient
can occur at any time, but usually presents during the first year of life. More that 70%
of healthy individuals have antibodies by the age of 4 years.
,-+
:::; b. 10. Mitra I stenosis
(I)
Symptoms of mitral stenosis may appear within 3-4 years of rheumatic fever or may
z
(I) be delayed for decades. Symptoms depend on the presence of pulmonary hypertension
,,
0
with low cardiac output (weakness, fatigue), and then, when the right ventricle fails,
symptoms of congestive cardiac failure (hepaton1egaly, peripheral oedema).
3
CJ
,-+ c. 7. Gastroesophageal reflux
m This history is consistent with aspiration secondary to a diagnosis of gastroesophageal
X
CJ
reflux. Other causes of aspiration which must be considered include trachea-oesopha
3 geal fistula, oropharyngeal incoordination or laryngeal cleft. Investigations may include
passage of the nasogastric tube, a pH probe study, a barium swallow, videofluoroscopy
and feeding assessment, bronchoscopy, laryngoscopy and endoscopy.
Gastroesophageal reflux may be treated medically but sometimes if severe, may require
fundoplication and gastrostomy feeding.
'"ti
Ill
Fig 10.5
A 3-day-old baby boy was reviewed on the post-natal ward following an episode of
generalised "jerking". He had been born at term in good condition by spontaneous
vertex delivery (SVD) and there were no clinical concerns prior to this episode. On
examination, he was noted to be dysmorphic (Fig. 10.5) and jittery.
Serum biochemistry was as follows:
Na 135 mmol/I
Ca 1.27 mmol/I
PO4 3.35 mmol/I
Mg 0.8 mmol/I
Glucose 3.6 mmol/I
i. Beckwith-Wiedemann syndrome
ii. Russell-Silver syndrome
iii. Autosomal dominant neonatal seizures
iv. DiGeorge syndrome
v. William's syndrome
b. What other investigations should be requested?
i. EEG
ii. Organic acids
iii. Echocardiogram
iv. Parathyroid hormone
v. Ammonia
vi. Lumbar puncture
391
10.s
a. iv. DiGeorge syndrome
b. iii. Echocardiogram
0 iv. Parathyroid hormone
C
(D
� These results demonstrate low calcium with high phosphate. The likely diagnosis is
a·
:::s hypocalcaemic hypoparathyroidisn1 as part of DiGeorge syndrome.
Vl
Q) This can be confirmed by fluorescent in-situ hybridization (FISH) analysis for chro
:::s
a. mosomal deletion at 22q11.2.
)>
:::s
Vl
Further investigations should include an echocardiogran1 for evidence of congenital
heart disease, a CXR/ chest ultrasound scan for absence of the thynms, T-lymphocyte
""'I
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subsets and PTH levels.
-+,
0
""'I
The DiGeorge syndrome forrn_s part of the constellation of abnonnalities collectively
,-+ termed CATCH 22 (cardiac defects, abnonnal facies, thymic hypoplasia, cleft palate,
::::,
(I) hypocalcaemia). These occur as a result of maldevelopment of the third and fourth
z
(I)
pha1yngeal pouches in early ern-6tyonic life.
.,,
0
A spectrum of clinical findings occurs. This classically includes conotruncal cardiac
abnormalities, abnormal facial appearance (downward slanting palpebral fissures, a small
3 chin, broad forehead and abnormal ears), absence of the thymus (with resultant T-cell
OJ
,-+ mediated immune deficiency), and absence or hypoplasia of the parathyroid glands
m (leading to hypocalcaemia).
><
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3 Less well recognised are learning, speech, feeding and psychiatric disorders. The
22q11.2. deletion can be inherited as an autosomal dominant disorder (as in this family)
or arise as a de-novo deletion or translocation.
392
s:
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n
n
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:::r:
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.....
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Fig 10.6
A 3-year-old boy presented with a 4-day history of being generally unwell: lethargic
with a decreased oral intake. On day 2 of the illness he developed a sticky right eye.
His GP prescribed chloromycetin eye drops for conjunctivitis. Hours after using the
drops his mother noticed a squint; she assumed this was due to the treatment, which
she continued. She also noticed that he was very unsteady on his feet. He was no
better 3 days later and the GP referred the child to A&E. On arrival the boy had a GCS
of 14, was irritable, lying curled up on his side with his neck hyperextended, and was
afebrile, pulse 119, blood pressure 95/55 with a right-sided 6 th cranial nerve palsy. The
child was uncooperative for the remaining neurological assessment; however, reflexes
seemed normal but with equivocal plantar responses. The fundi could not be visualised.
FBC, U&Es, blood cultures and serum for virology were taken.
i. Orbital cellulitis
ii. Subdural haemorrhage
iii. lntracranial space-occupying lesion
iv. Meningitis
v. Benign intracranial hypertension
b. What further tests would you want initially?
i. Lumbar puncture
ii. Ophthalmological review
iii. Urine toxicology
iv. CT scan
V. EEG
vi. Serum calcium and magnesium
c. What treatment would you initiate?
i. Steroids
ii. i.v. benzylpenicillin
iii. i.v. acyclovir
iv. Mannitol
v. i.v. cefotaxime
393
ANSWERS 10.6
a. iii. lntracranial space-occupying lesion
iv. Meningitis
0 b. i. Lumbar puncture
{:
Cl)
iv. CT scan
�
5· C. iii. i.v. acyclovir
:J
Vl V. i.v. cefotaxime
OJ
::, This previously well 3-year-old child presented with a vague history of being generally
a..
unwell vvith ataxia and a new squint. The positive findings on examination were
)>
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extreme irritability, the neck hyperextension and the squint. There was no history of
fever and vital signs were stable.
After the initial bloods were taken he began on i.v. cefotaxime and acyclovir to cover
-n
0
.., bacterial meningitis and herpes encephalitis. However, his signs fitted well with a space
,-+ occupying lesion and he underwent urgent CT scan under general anaesthetic. This
::::;
Cl) ,vas normal with no evidence of raised intracranial pressure. Whilst under anaesthetic,
z
Cl)
his fundi were visualised (normal) and a lumbar puncture was performed. The CSF
� contained 840 white cells (80% neutrophils) and 60 red cells. CSF glucose was
,,
0
2.4 rnrnol/1 (serum 5.5 mmol/1) and protein was 40 g/1. Multiple other investigations
3
OJ
were done to look for an acute cause of his ataxia including a n1etabolic screen, thyroid
function and Lyme disease serology.
,-+
m After 24 h he was markedly better. Apart from_ the squint he was back to normal by
><
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day 4. Intravenous antibiotics and anti-virals were stopped after 1 ,veek. At this tin1e
3 the CSF PCR result was received which was positive for meningococcus.
Unilateral cranial nerve palsy is a recognised cornplication of bacterial meningitis but
most commonly the facial nerve is involved. The palsies tend to be transient.
A boy of 7 years attends a clinic showing rigidity in his routines and getting upset
when they are changed. He gets agitated if he misses programmes on television and
gets temper tantrums when he is asked to do things or to change his routine. He
insists that stories have to be read to him in a particular way. On enquiry it is clear that
he was late in showing imaginative play; however, his early development was otherwise
normal. He lacks close friends and when attempting to play with his peer-group, he
insists on doing things in a certain way. If rules are changed he is unhappy and
sometimes aggressive. He avoids eye contact, his language tends to be formal and N
pedantic and he does not follow conversations well. His speech is loud, fast and often
delivered in a monotone way reflecting his interests at length without regard to the
listener's attention. He has acquired extensive knowledge about aeroplanes and other
circumscribed interests while his application to school work is inconsistent, despite
above average ability on formal assessments.
What diagnosis is suggested from this information?
i. Dyspraxia
ii. Obsessive-compulsive disorder
iii. Autism
iv. Asperger syndrome
v. Rett's syndrome
vi. Childhood-onset schizophrenia
395
ANSWER TO 10.7
iv. Asperger syndrome (AS)
,0 The following are the criteria for the diagnosis of AS (DSM-IV):

C
(I) 1. Severe and sustained impairment in social interaction manifested by at least two
� of the following: impairment of non-verbal behaviour, for exarnple eye-to-eye
o· gaze, facial expression, body postures and gestures to regulate social interaction;
:J
VI
QJ
failure to develop peer relationships; lack of spontaneous seeking to share enjoy
:J ment, interests, or achievement ,vith other individuals; and lack of social or
Cl.
emotional reciprocity
)>
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VI
2. Restricted repetitive and stereotyped pattern of behaviour, interests, and activities
as manifested by at least one of the following: encon1passing preoccupation with
""'I
VI
at least one stereotyped and restricted pattern of interest that is abnornial either
-n in intensity or focus; inflexible adherence to specific, non-functional routines or
0
""'I rituals; stereotyped and repetitive motor mannerisms; and persistent preoccupation
,+
::::; vvith parts of objects
(I)
3. Clinically significant impairment in social, occupational or other areas of
z
(I) functioning
4. No significant delays in cognitive development, in the developrnent of self-help
"TI
0 skills, adaptive behaviour (other than social interaction) and curiosity about the
3OJ environm.ent
,+ 5. No clinically significant delay in language developrnent
m 6. Criteria not met for other specific pervasive disorders or schizophrenia
X
OJ
3 Other conditions to be considered include other pervasive developrnental disorders
such as childhood disintegrative disorder, autism. or pervasive disorders not otherwise
specified. In a girl, Rett syndrom.e might be a differential diagnosis. All pervasive
developmental disorders are characterised by im.pairm.ent of reciprocal social interaction,
verbal and non-verbal com.munication skills or the presence of stereotyped behaviour,
interests and activities. Further differential diagnoses include schizoid personality dis
order, obsessive-compulsive disorder and very rarely, childhood-onset schizophrenia.
AS is a specific condition on the autism "spectrum." and is n10re con1111on in males.
In contrast to childhood autism, there are no significant delays in early language devel
opment. Symptoms in autistic disorders have to be present prior to the age of 3 years;
AS is generally diagnosed later, typically in mid-childhood. Childhood disintegrative
disorder is defined by developmental regression after at least 2 years of normal develop
ment. AS and OCD share repetitive and stereotyped patterns of interests in their
diagnostic criterion. Individuals with AS exhibit qualitative impairment in social inter
action and a more restricted pattern of interests. AS is distinguished from schizoid
personality disorder by stereotyped behaviours and interests and by a more severely
impaired social interaction.
396
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Fig 10.8.A
Fig 10.8.B
A 2-year-old is referred for a medical examination by his GP and social services, after a
deformity of his right ankle was noted. The parents had no explanation to offer. He is
still breast fed and there have been concerns raised previously about his mildly delayed
motor development. He is one of three children who live with their parents and other
families in a large isolated house. The health visitor, who is not allowed to visit,
describes their lifestyle as "alternative".
On examination he is well grown, with no signs of trauma. He has swollen wrists and
an obvious abnormality of his right ankle. X-rays are taken (see Figs 10.8.A & 10.8.B).
a. What features are shown on the X-rays?
i. Poor bone mineralisation
ii. Pathological fracture
iii. Rachitic rosary
iv. Delayed bone age
v. Metaphyseal splaying
vi. Callous formation
b. What investigations would you do to help confirm the diagnosis?
i. Bone scan
ii. Serum phosphate
iii. Urinary phosphate
iv. Skeletal survey
V. DEXA scan
vi. Serum uric acid
c. What is the major danger of treatment?
i. Secondary hypoparathyroidism
ii. Seizures
iii. Nephrocalcinosis
iv. Hypocalcaemia
v. Tetany
397
ANSWERS TO 10.8
a. i. Poor bone mineralisation
v. Metaphyseal splaying
b. ii. Serum phosphate
v. DEXA scan
c. iii. Nephrocalcinosis
a,
The X-rays show the main features of rickets:
::J Generalised poor bone mineralization
a.
Deformity of long bones and delayed development of epiphyses
)>
::J "Cupping", "fraying" and "splaying" of the metaphysis (i.e. concave, irregular
metaphyseal margins with a greater than normal diameter)
"""'
(I)
I"
The diagnosis of "rickets" is confirmed by finding a high serum alkaline phosphatase,
-
0
"""' a low phosphate and low/normal calcium. Rickets is further classified in Table
,-+ 10.8.1.
::r
(l)
z In the case described, results were consistent with vitamin D deficient rickets. Further
(I) history confirmed risk factors for vitamin D deficiency:
.,,
0
Prolonged breast feeding
Minimal exposure to sunlight
3
a,
Poor dietary sources of vitamin D
,-+
m It is important to exclude malabsorption, and screen other family 1nernbers.
><
a, Treatment consists of high dose vitamin D (1000-5000 iu/day) until alkaline phos
3 phatase is in normal range, then vitamin D intake maintained at "normal" level of
400 iu/day. Success of treatment is confirmed by biochem_ical parameters returning to
normal. A repeat X-ray will show radiographic evidence of irn.provement.
The risk of high dose vitamin D is hypercalcaemia and consequent nephrocalcinosis - it
is important to monitor serum calcium levels during treatment.
Table 10.8.1
25-HCC 1,25- DHCC P04 PTH :},

Vitamin D deficiency (i.e. lack of dietary vit. Low Low Low High/normal
D, lack of sunlight, malabsorption)
---,~---------·�- � --
- �,-�-- __ ____
,,,
Vitamin D dependent rickets Type I (i.e. Normal Low Low Increased/normal

defect in Vit D metabolism)
Vitamin D dependent rickets Type II (i.e. vit Normal Normal Low Increased/normal
D receptors "defective")
Vitamin D resistant (hypophosphataemic) Normal Normal Very low Normal L :

rickets (i.e. X-linked
hypophosphataemic rickets, renal P04
loss - Fanconi's, etc.)
398
A 3-year-old girl was admitted with a short history of pyrexia, vomiting and a possible
seizure at home. Her mother gave a history of previous illnesses associated with
drowsiness and vomiting. She had mild developmental delay and poor speech. On
examination, she was unrousable. A full infection screen including lumbar puncture was
negative.
Initial bloods showed:
Hb 12.7 g/dl Na 138 mmol/I
wee 17 X 109/I K 3.8 mmol/I
Platelets 270 x 109/I Urea 1.4 mmol/I
CRP 77 Creatinine 62 µmol/I
Glucose 4.5 mmol/I LFTs normal
Ammonia 412 µmol/I Lactate 3.98 mmol/I
Venous gas: pH 7.411, pCO 2 34.6 mmHg, bica1·bonate 22.9 mmol/I
Cranial CT was normal
i. Urea cycle disorder
ii. Mitochondrial disorder
iii. Reye's syndrome
iv. Organic aciduria
v. Medium chain acyl-CoA dehydrogenase deficiency
b. What treatment may be needed?
1. Forced alkaline diuresis
ii. Stop protein intake acutely
iii. Restrict protein intake to 2 g/kg/day
iv. Dialysis or haemofiltration
v. Sodium benzoate
vi. Calcium benzoate
vii. Dexamethasone
399
a. i. Urea cycle disorder
b. ii. Stop protein intake acutely
D iv. Dialysis or haemofiltration
C:
ro v. Sodium benzoate
�
6' The diagnosis is a urea cycle disorder, which is suggested by the high arnn10nia (normal
:l
Vl
0.,
level 10-47 µn101/l), the metabolic alkalosis, and the low urea.
:l
a. The differential diagnosis of hyperammonaemia would include an organic aciduria and
)> Reye syndro1ne.
:l
�
ro
The histo1y given of recurrent illnesses associated with vomiting and drowsiness should
prompt a search for underlying inborn errors of metabolism. In infants, feeding prob
-+, lems, von1iting, failure to thrive and chronic neurological symptoms may be noted.
0
., Episodes of encephalopathy occur with von1iting, drowsiness, ataxia and irritability,
,-+
::; progressing to con1a. Seizures and developmental delay are common. Because of the
(D
importance of identifying treatable n1etabolic disorders, early investigation of patients
z
(D presenting stuporose or obtunded should not be delayed.
.,,
0
Management involves resuscitation: ABC. Protein intake should be stopped immedi
3
0.,
ately. Fits should be appropriately treated. Treatn1ent of hyperammonaemia may involve
dialysis or haemofiltration, especially if the an1n1onia is over 400 µn101/l. Sodiun1 ben
,-+
m zoate, sodium phenylacetate and arginine are also used.
><
OJ
Other investigations include plasma and urine amino acids, which may show charac
3
teristic changes. Liver biopsy allows precise identification of the enzyn1e deficiency in
the urea cycle disorders. This girl had carbamyl phosphate synthetase deficiency.
400
A 2-year-old boy, with recurrent glue ear, who was fully immunised, including
Haemophilus inf!uenzae type b (Hib vaccine), was admitted with a right-sided preseptal
cellulitis. His corneal swab grew Haemophilus inf!uenzae type b.
s:
;::o
('\
'"O
How should this child's immunological status be further assessed? ('\
I
SELECT ONE ANSWER ONLY '"O
0,
i. Hib antibodies checked, and reimmunised if low """I
r+
ii. Serum immunoglobulins, and investigate further if low N
iii. No antibody check necessary, but revaccinate
iv. No investigations and no vaccination necessary
401
iv. No investigations and no vaccination necessary
0 No assessment necessary. Hib vaccine protects against capsulated strain infections only,
C:
(I) such as seen in meningitis, osteomyelitis, and epiglottitis. It does not protect against
otitis media and conjunctivitis, ,vhich are caused by uncapsulated strains. This is because
V,
r+
6' the vaccine is made by conjugating polysaccharide capsular antigen to a carrier protein.
:::::i
V,
OJ
This irn_proves vaccine innnunogenicity, especially in children less than a year. Similar
:::i conjugation techniques were used to produce the n1eningococcal C vaccine.
a.
)>
:::::i
�
(I)
""I
V,
-+,
0
"""I
r+
::::,
(I)
z
(I)
�
-n
0
3
OJ
r-+
m
><
OJ
3
402
s:
.,,0
;:,:J
(')
:r:
.,,
a,
.....
r+
N
Fig 10.11
An 8-year-old girl presented with a 6-month history of increasing lethargy and weight
loss of 4 kg. Her parents had noted that she had cool extremities and blue cheeks and
lips. Recently, she had been fainting at school following exercise and she was also
noted to have facial tics and abnormal arm movements. She had been adopted at the
age of 6 months and little was known about her perinatal and postnatal period. She
had been under follow-up for global developmental delay and learning difficulties. Her
only admission to the hospital was at the age of 9 months with bronchiolitis. On
examination, she was not dysmorphic. Both her weight and height were below the
0.4th centile. Her lips appeared to be mildly dusky but she was not clubbed. A right
parasternal heave was palpable. On auscultation, her first heart sound was normal and
her second was accentuated but no murmurs were heard. Her chest was clear and only
the liver tip was palpable. Her ECG is shown.
What does the ECG show?
i. Left ventricular hypertrophy
ii. Right axis deviation
iii. Right ventricular hypertrophy
iv. Superior axis
v. ST elevation
vi. Left axis deviation
vii. Right atrial enlargement
viii. Long QT interval
403
ANSWERS CASE 10.11
ii. Right axis deviation
iii. Right ventricular hypertrophy
D vii. Right atrial enlargement
C
�
{D
o·
:J
ECG shmvs right axis deviation, right atrial enlargement and right ventricular hyper
trophy; very unusual in a child of her age indicating elevated right-sided pressures.
V)
OJ
Investigations helpful in primary pulmonary hypertension P
( PH) diagnosis: CXR.., echo,
:J V/Q scan, thrombophilia screen, autoantibodies, ESR, FBC+film, and chromosomes.
C.
)> PPH may be primary or secondary to underlying disease:
:J
1. Cardiac causes: supramitral ring/web, untreated AVSD
..,
(D 2. Respiratory causes: chronic lung disease, CF, chronic upper airway obstruction
V) (large tonsils and adenoids)
-
0
.., 3. Thro1nboembolic cause: iatrogenic, coagulopathy, schistosomiasis
r-+ 4. Connective tissue disorder: systemic lupus erythematosus
::::r
(D
PPH is raised rnean pulmonary arterial pressure >25 n1111Hg at rest (>30 mmHg during
z
(D exercise) with no identifiable cause; rapidly progressive, it causes disabling symptoms,
::§:
,,
0
leading to death if untreated. Non-specific symptoms are usual: breathlessness (rnost
common), chest pain and syncope. Often 3 years pass between first syn1ptoms and
3OJ diagnosis. CXR, ECG and respiratory referral should be requested; the former is usually
r-+ abnormal (85%), showing enlarged proxim.al pulmonary arteries ("proximal pruning")
m and the ECG shows right ventricular hypertrophy. Supportive treatment rather than
><
OJ curative is usual:
3 OA7gen therapy: hypoxaemia causes pulrn.onary vasoconstriction and thus worsening
of pulmonary hypertension
Anticoagulation: reduces pulmonary arterial throrn.bosis and hypercoagulable state
present in pulrn.onary hypertension
Vasodilator therapy: using Ca antagonists, ,vhich cause pulmonary and syste1nic
vasodilatation
Long-term. prostacyclin therapy: potent endogenous vasodilator, which inhibits
platelet aggregation, thought to be associated with remodelling puhnonary vascular
bed, with subsequent reduction in endothelial cell injmy and hypercoagulability
Atrial septostorny: a palliative procedure, which acts as a "blmv off valve" during
hypertensive crises, the child shunts right to left across the atrial communication
becoming cyanotic, but maintaining cardiac output.
Lung transplantation improves quality of life and survival.
AP wave of >2.5 mm tall reflects right atrial enlargement. AP wave of >120 ins in
duration reflects left atrial enlargement.
Right ventricular hypertrophy is demonstrated by:
right axis deviation
neonatal R/S progression across the chest leads after the newborn period (i.e.
don1inant R in V1 and dorn.inant S in V6)
abnormally large R wave in V1 or S in V6
Upright T wave in V1 after day 3 and under 6 years of age
404
A 14-year-old Asian girl was referred by her GP to the paediatric surgical team with a
diagnosis of possible acute appendicitis. She had been experiencing recurrent bouts of s;:
colicky abdominal pain (mainly right sided), loose stools and loss of appetite for the ;:7J
('I
preceding 2 days. Examination revealed a pale, thin girl who was obviously unwell and -,:,
(')
in pain. She was mildly febrile and normotensive, with a pulse rate of 90 bpm. Her I
abdomen was generally tender on palpation, more so in the right iliac fossa, but there -,:,
!l>
was no guarding or rebound tenderness. She had numerous mouth ulcers. On plotting ;:l.
the girl's height and weight, she was below the third centile for both. On further N
questioning, her father mentioned that she had been experiencing these recurrent
bouts of abdominal pain and diarrhoea for the previous 6 months.
What is the most probable diagnosis for this girl?
i. Irritable bowel syndrome
ii. Sub acute appendicitis
iii. Vitamin B deficiency
iv. Ulcerative colitis
v. Lymphoma
vi. Crohn's disease
405
vi. Crohn's disease
Any history of weight loss, rectal bleeding, urgency, tenesmus, peri-anal symptoms and
nausea and vomiting, as well as joint pains, skin rashes and episodes of unexplained
fever should be established. It is also important to enquire about whether the girl has
started to develop signs of puberty, i.e. whether she has started the n1enarche.
OJ The n1.ost probable diagnosis for this girl is Crohn's disease. Investigations should
:::::l
0.. include:
)> 1. Blood tests: FBC, acute phase reactants (CRP, ferritin), ESR, serum and red cell
:::::l
folate, serum vitamin B12, LFTs and serum albumin, serology for Yersinia entero
�
ro pathica and Entamoeba histolytica
""'I
VI
2. Stool tests: stool microscopy of fresh stool (ova, cysts, parasites, Giardia and
-I-,
0
""'I
amoebae), stool culture (Salmonella, Shigella, Campylobacter, enteropathogenic
r-+ E. coli and Clostridium difficile toxin)
:::r
ro 3. Imaging: abdominal ultrasound, barium meal and follow-through, white cell
z scan
ro
:;§: 4. Upper gastrointestinal endoscopy and colonoscopy (with ileoscopy)
.,,
0 Crohn's disease presents usually over the age of 10 years, but more children are pre
3OJ senting earlier. In childhood and adolescence the disease often manifests similarly to
r-+ adults, but children sometimes present without GI symptoms, showing only growth
m failure, pyrexia of unknown origin and pseudo-appendicitis. Diagnosis is often delayed
><
OJ
by up to 2 years, especially with primary systemic features such as growth failure,
3 thought to be caused by malnutrition as well as the inflammatory process. Inflammation
leads to the release of tumour necrosis factor-alpha, postulated to have a direct effect
on the epiphyseal growth plates. GI symptoms include: abdominal pain, anorexia,
nausea, vomiting and diarrhoea. Abdominal pain (often brought on by eating) is char
acteristically peri-umbilical and colicky. Anorexia may be so severe that anorexia
nervosa is sometimes diagnosed. Chronic constipation can also be an important feature.
Vomiting and diarrhoea may have an acute onset and suggest acute gastroenteritis.
Differentiation from ulcerative colitis may be difficult if bloody diarrhoea results from
colonic involvement. Physical examination may reveal retarded growth and develop
ment, delayed puberty, facial pallor with characteristically dark skin beneath the eyes,
frank oral ulceration and angular cheilitis. Other feature include a palpable abdominal
mass, painless anal fissures and a peri-anal abscess or a fistula-in-ano. Children may
present with a severe attack and a "toxic" appearance with pallor, tachycardia and
s,,vinging fever. A secure diagnosis depends on histological findings (total colonoscopy,
with entry into the ileum, usually revealing sarcoid-like, non-caseating granulon1.ata in
the mucosa or submucosa); barium meal and follow-through should be performed to
visualise the ileum adequately. Upper GI endoscopy may be used to differentiate
between Crohn's disease and ulcerative colitis.
406
s:
:::0
0
-0
r,
:::c
-0
OJ
;:::i
N
Fig 10.13
A 10-week-old boy presented with a 3-day history of being off his feeds and 2 days of
vomiting. He had had several self-limiting episodes of pallor and tachypnoea over the
previous few days. He had been born at full term and was being breast fed and
making appropriate developmental progress. On examination, he was pale and sweaty
with a delayed capillary refill time. His heart rate was over 240 bpm. An ECG was
obtained.
a. What does the ECG show?
i. Superior axis
ii. Ventricular tachycardia
iii. 1 : 1 AV conduction
iv. Sinus tachycardia
v. Supraventricular tachycardia
vi. Broad complex tachycardia
b. What condition, diagnosable on ECG, are these findings associated with?
i. Wolff-Parkinson-White (WPW) syndrome
ii. Atrioventricular septal defect
iii. Salbutamol toxicity
iv. Hypertrophic obstructive cardiomyopathy
v. Pericarditis
407
a. iii. 1 : 1 AV conduction
v. Supraventricular tachycardia
b. i. Wolff-Parkinson-White (WPW) syndrome
The differential diagnosis from the history alone must include sepsis and cardiac failure,
as ·well as a cardiac arrhyth1nia. The ECG here shows supraventricular tachycardia with
OJ
a rate of 300 bpm, a narrow QRS con1plex with 1 : 1 AV conduction.
a.
::,
SVT is the n1ost common abnormal arrhythmia in infancy and childhood, and the
)> majority of children have structurally normal hearts. In infants, n1ost attacks occur
::,
V, before 6 months of age and the prognosis is excellent. Attacks may be transient and
�
(I) undetected, and if attacks last for n10re than 24 h, heart failure usually ensues and
'""I
V, treatn1ent becomes urgent. In older children, episodes may recur over n1any years and
-
0
'""I
may be refract01y to treatment necessitating ablation of the access01y connection.
r-1-
:::, Treatment is dependent on the presence of shock on presentation. If shock is present
(I)
then cardioversion is the treat1nent of choice. Cardioversion in an unconscious or
z
(I) anaesthetised child is given using a synchronised shock delivered at 0.5/1/2]/kg. Other
� treatments include vagal 1nanoeuvres, i.v. adenosine, i.v. digoxin and flecainide. Vagal
"TI
0 rnanoeuvres, such as eliciting the diving reflex by submerging the face into icy water,
3 can be ve1y effective in aborting an attack. Adenosine given in an i.v. bolus acts to
OJ
r-1- prevent conduction through the AV node. Intravenous digoxin or flecainide can be
m used under the supervision of a cardiologist.
><
OJ
3 SVT is associated with WPW syndro1ne. A large proportion of infants and children
with parm,7s1nal SVT shmv ECG features of WPW syndrome a short PR interval,
broad QRS complex and delta wave. The accessory pathway bypasses junctional tissue
that allows a circuit to be forn1ed that facilitates re-entry tachycardia.
The access01y pathway may go from. the left atrium to the left ventricle (type A) simu
lating right bundle branch block or from the right atrium to the right ventricle (type
B) simulating a left bundle branch block pattern.
408
A 5-month-old Caucasian baby girl was admitted to the local hospital with a 2-week
history of being generally unwell with intermittent pyrexia. On the day of referral to the �
hospital she had a generalised tonic clonic convulsion. She was born at term by normal ::JJ
("'\
vaginal delivery. The mother had been in contact with her partner, who had a chronic "'O
n
cough. Initial investigations done showed: :::r:
Hb 11.6 g/dl "'O
Q)
. WBC 27.5 X 109/I '""I
r+
Neutrophils 12.9 x 109/I N
Lymphocytes 11.6 x 109/I
CRP 22.5 mg/I (<10)
Blood glucose 4 mmol/I
CSF gross - slightly turbid
CSF Microscopy 115 WBC/mm3 (80% polymorphs and 20% lymphocytes)
CSF Protein 1.7 g/I
CSF Glucose 0.2 mmol/I
CT scan - bilateral dilated ventricles
What diagnosis should be considered most likely?
i. CNS vasculitis
ii. Medulloblastoma
iii. Cerebral leukaemic infiltration
iv. Herpes simplex encephalitis
v. Viral meningitis
409
.0 Bacterial or tuberculous meningitis (TBM) would be your main differential diagnosis

C with the CSF findings and history of contact with partner having a chronic cough.
(I)
� The CSF findings shmv lmv glucose, mildly elevated protein and mixed cells with
o· polymorphonuclear cells predominating at this stage.
�
::J
ru
::J
Further tests to assist in making the diagnosis include CSF Gram-stain and Ziehl-Nielson
a.. stain to look for acid-fast bacilli (AFB), CSF culture for bacteria and rnycobacterium
)> tuberculosis, Mantoux test, PCR for mycobacterial DNA, CXR and early-n1orning
::J
nasogastric aspirates. Mantoux test is positive in up to 90% of TBM and therefore is very
� useful. Mycobacterial DNA in CSF may be a more sensitive test than CSF stain and culture
.,
(I)
� as AFB are seen in only 25% of CSF smears and about 50% of CSF vvill grow the bacilli
-+,
Q after several weeks. Sensitivity for DNA PCR is about 90%.

,-+
:::r Until the diagnosis is confinned the child should be conunenced on broad-spectruni
(I)
antibiotics and antituberculous drugs. Four-drug antitubercular treatment with steroids
z
(I) should be commenced. Postinfective hydrocephalus may need shunting. Public health
�
.,,
0
notification and screening of family are important additional measures.
3
OJ
This patient had tuberculous meningitis. The prognosis is related to the patient's condi
tion at the tin1e of treatment. In the early stages of the disease (i.e. prodronial phase)
,-+
m a 100% cure and a low incidence of sequelae can be anticipated. In cases where neu
X
OJ
rological signs and symptoms are present prior to commencement of treatment approxi
3 mately 50% survivors show neurological defects. In those presenting with altered
consciousness levels a 50% survival has been reported despite treatment and most sur
vivors have pern1anent handicap.
Tuberculosis constitutes a major cause of death worldv,,ide. An estimated 1.3 million
cases of tuberculosis and 450 000 associated deaths occur annually in children. Recent
ti1nes have seen a resurgence of this infection in the UK not only in the ethnic rninori
ties but also in the Caucasian population. Children show a high predisposition to
developing extrapulmonary TB and its impact is greatest among infants and young
children who tend to develop n10re severe extra-puln1011ary disease, especially n1.enin
gitis and miliary TB. HIV increases the risk of TBM and needs to be considered in
these patients. Considering the resurgence of TB in the population, a strong index of
suspicion needs to be maintained to enable early diagnosis and treatment.
Table 10.14.
CSF analysis White cells/mm3 Protein (g/1) Glucose (mmol/1)
Normal <4 lymphocytes <0.4 >2.2 (or -2/3 plasma)

0 polymorphs
Acute bacterial 200-20 000 polymorphs 1-5 Usually low

meningitis
Tuberculous meningitis 25-100, mainly Usually 1-2 but may Usually low
lymphocytes except be much higher
in early stages
when mainly
polymorphs
Cryptococcal meningitis -50 (0-800) mainly -1 (0.2-5) Normally low, average .7

lymphocytes
Viral meningitis 5- > 1000, mainly Usually <1, may be Normal but may be low in
lymphocytes except greater in severe some cases of
in early stages cases mumps and HSV1
410 when mainly
polymorphs
A 5-year-old girl was admitted with a 5-day history of sore throat and increasing
jaundice. She had not had abdominal pain or diarrhoea, but her urine was darker than
usual, and her stool was "orange". Two weeks previously she had travelled to Florida
and Egypt. Examination revealed a pale, but active, jaundiced child, with a temperature
of 37 ° (, pink ears and throat, and no other abnormality noted. Her blood results are as
follows:
Hb 5.4 Na 136
MCH 29 K 4.2
MCV 87.4 Urea 4.6
wee 13.7 Creatinine 47
Platelets 96 Bilirubin 62
Direct Coombes' negative
Antibody screen negative
Protein 69 ALT 12
Albumin 42 ALP 174
Throat swab grew Mycop!asma pneumoniae. Infectious mononucleosis screen was
negative and G6PD screen was normal.
a. Which of the following diagnoses is excluded by the above results?
i. Autoimmune haemolytic anaemia (Mycop/asma)
ii. Viral hepatitis
iii. Hereditary spherocytosis
iv. G6PD deficiency
b. What further investigation would you do to help make a diagnosis?
i. GAL-1-PUT
ii. Osmotic fragility test
iii. CT scan abdomen
iv. Stool for bacteriology
v. Bone marrow aspirate
The next day the child became lethargic and was noted to be short of breath on
exertion. Hb was 5.1. Decision was made to give a blood transfusion. After receiving
40 ml of blood, her temperature increased from 37.5° ( to 38.5°C.
c. What is the most likely cause of the temperature?
i. Overheated blood
ii. Sepsis
iii. Transfusion reaction
iv. Graft versus host disease
v. Line infection
411
a. i. Autoimmune haemolytic anaemia (Mycoplasma)
b. ii. Osmotic fragility test
c. iii. Transfusion reaction
To help make a diagnosis other information required includes:
recent drug history
OJ racial origin
:::s previous episodes of jaundice and past medical history
0..
family history of jaundice
)>
:::s
V,
infectious diseases contact history
ingestion of fava beans or broad beans
ro
"""I
V,
hepatosplenomegaly
-
0
"""I
These blood results den10nstrate a non-autoinunune haen1olytic anaemia (HA) and
,-+ thrombocytopaenia. Mycoplasma can cause a HA, but it is an autoimnume HA char
:y
ro acterised by a positive direct Coombs, where antibody typically reacts with the red
z cells at 4 ° C (cold type); so this infection is not the cause of this anaemia. An osmotic
ro
fragility test is needed to exclude hereditary spherocytosis. There n1ay be a farnily
"TI history as it is inherited as autosomal dominant, variable expression. The G6PD screen
0
3
OJ
will need to be repeated ,vhen the child is better. G6PD is still a possible diagnosis
despite the normal screen. G6PD levels may be normal during haen1olytic episodes
,-+
m because of increased red cell turnover, so if norn1al, test again when acute haen10lysis
>< is over. If a diagnosis is made, treat with folic acid and give advice to avoid exacerbat
OJ
3 ing factors (anti-malarials, paracetamol, penicillin, fava and broad beans). Siblings should
be screened.
If a fever develops during a transfusion, the most likely diagnosis, and one that needs
urgent management, is a transfusion reaction. Managen1ent of a transfusion reaction:
stop transfusion; reassess; look for focus of infection; if none, consider a possible trans
fusion reaction; ensure the child is cardiovascularly stable, look for signs of shock
(delayed cap refill time, tachycardia, and later hypotension), and treat. Check that the
identity of the recipient is the sarne as that stated on the com_patibility label and that
this corresponds with the blood being transfused; send blood from the child, and the
rest of the blood being transfused, to the laboratory for culture to exclude bacterial
conta1nination. Also:
repeat group and cross-n1atch on pre- and post-transfusion samples
do a direct Coombs on the post-transfusion sample to look for antibody on the red
cell surface (if positive, this indicates a transfusion reaction; also positive with
autoinmrnne HA, drug-induced HA, and haemolytic disease of the newborn)
check plasrna for haen10globinaemia
look for evidence of disseminated intravascular coagulation (clotting screen, increased
fibrinogen, degradation products)
examine urine for haemoglobinuria
take further sam_ples of blood several hours later to look for falling haemoglobin
and rising bilirubin
if no positive findings look at the patient's serun1 5-10 days later for red or white
cell antibodies
412
A 4-year-old boy presents with a 2-week history of fever, lethargy and an intermittent
rash. On examination, he is clinically anaemic and has cervical lymphadenopathy, a
warm effusion in the left knee and a macular, salmon-pink rash over his trunk. His
temperature chart clearly shows twice-daily fevers that exceed 41°C and do not reduce
with non-steroidal anti-inflammatory drugs (NSAIDs). The GP has reported his CRP level
as being elevated at 115.
What are your differential diagnoses at this stage?
i. Polyarteritis nodosa
ii. Measles
iii. Systemic-onset juvenile idiopathic arthritis
iv. Acute lymphoblastic leukaemia
v. Rheumatic fever
vi. Kawasaki syndrome
vii. Rubella
413
iii. Systemic-onset juvenile idiopathic arthritis
iv. Acute lymphoblastic leukaemia
.Xfj
C
(I) Differential diagnoses at this stage should include systemic-onset juvenile idiopathic
� arthritis (JIA), infection and acute lyn1phoblastic leukaen1ia.
6"
::l
V'l
QJ
Systemic-onset JIA
a.
::l
The definition of a JIA is a chronic arthritis persisting for 1nore than a minimum of 6
)> consecutive weeks in one or more joints. Systemic-onset JIA usually comn1ences before
::l
V'l the age of 5 years, although occasionally presents in older children and adults. It
accounts for approxin1ately 10% of children ,vith JIA. The systemic features may
'""I
V'l precede arthritis by weeks or months. The features include a high spiking temperature
-h
0
'""I
(often twice daily, dipping below the baseline in between spikes), a classic rash that
,-+ consists of discrete, salmon-pink macules that tend to be n1igratory and visceral involve
:::,
(I) n1ent (including hepatosplenomegaly, lymphadenopathy and pericarditis). The children
z
(I)
often appear acutely unwell. There may be a 1nunnur heard on auscultation. Investiga
tions -which should be carried out initially include:
,,
0
FBC and fihn
3OJ blood cultures
CXR
r+
m
viral screen and autoimmune profile
><
OJ Acute treat1nent of this child involves broad-spectrum antibiotics until the infection
3 screen has been obtained, non-steroidal anti-inflammatory drugs (NSAIDs), and oral
or i.v. steroids once infection has been excluded. Gentle, paced physiotherapy and
nutritional support should be given if necessary.
Diagnosis of syste1nic-onset JIA is difficult initially, particularly in the absence of arthri
tis. It is important to exclude malignancy, sepsis, inflammatory bmvel disease and vas
culitides. Laboratory tests are helpful in exclusion of other entities but are not specific
in systemic JIA. The course and duration of this disease is variable. The systemic fea
tures tend to subside during the initial months or years but may recur with flares of
the arthritis. The arthritis may become aggressive, affecting many joints and occasionally
necessitating their replacement.
Treatment is multidisciplinary. Medications include NSAIDs, prednisolone (i.v., pulsed,
oral or intra-articular) and second-line therapy (methotrexate, cyclophosphamide and
anti-tumour necrosis factor). Approximately 50% of children recover com_pletely with
no significant disability in adult life.
414
Table 10.17.1
y
Biopsy
Positive Negative Total

"'ti
Blood test Positive 119 45 164 OJ
'""I
r-t
N
Negative 26 460 486
~-
Total 145 505 650
A group of clinicians wished to use a blood test to screen for a certain condition. In
order to determine the accuracy of this screening test, a comparison needed to be
made with a definitive test such as a biopsy. Six hundred and fifty individuals were
tested using both the blood test and the biopsy and the above results were obtained:
a. What is the specificity of the test?
i. 119/145
ii. 26/460
11i. 460/486
iv. 460-26/486
What is the negative predictive value for this test?
i. 460/650
ii. 26/460
iii. 460/486
iv. 460-26/486
415
ANS WIERS TO CASIE 10.11
a. i. 119/145
b. iii. 460/486
The prevalence is the proportion of subjects affected by the disease. The nun1ber that
actually has the disease is identified by those with a positive result fron1 the biopsy,
i.e. 145.
QJ Thus the prevalence of the disease is 145/650 = 0.223 or 22.3%.
:::I
0..
The sensitivity 1neasures how sensitive the screening test is for detecting the disease
)>
:::I
VI
-when it is actually present. The sensitivity for this test is 119/145 = 0.821 or 82.1%.
The specificity is the proportion of subjects that don't have the disease that are cor
....
<D
VI
rectly identified by the screening test as not having it. Therefore, the specificity is
--+,
0
.... 460/505 = 0.911 or 91.1%.
,-+
::r The positive predictive value is the proportion of subjects that have a pos1t1ve test
<D
result that do have the disease. So the positive predictive value for this example is
z
<D 119/164 = 0.726 or 72.6%.
,,
0
The negative predictive value is the proportion of subjects that have a negative test
3
QJ
result that don't actually have the disease. Therefore, the value will lie between 0 and
1. For this example, the negative predictive value is 460/486 = 0.947 or 94.7%.
,-+
m
><
QJ
416
Fig 10.18
A neonate born at 26 weeks' gestation was intubated in the labour ward, given
surfactant and ventilated. On day 2 the baby deteriorated, developing abdominal
distension and increasing oxygen requirements. Abdominal radiograph suggested a GI
perforation. After recovery it was difficult to establish feeds. Difficult i.v. access resulted
in the insertion of a Broviac line into the right internal jugular vein. This was
subsequently removed because of line infection. Two days later the baby collapsed.
Arterial blood gas showed a pH of 7.0, pC0 2 9 kPa, p0 2 3 kPa, HC0 3 22 mmol/1 and a
base excess of -6 mmol/1. The CXR is shown.
a. What does the X-ray show?
i. Right-sided pneumothorax
ii. Right-sided pleural effusion
iii. Right-sided consolidation
iv. Right-sided collapse
i. Chylothorax
ii. Pneumonia
iii. Hyaline membrane disease
iv. Pulmonary haemorrhage
417
CASE 10.18
a. ii. Right-sided pleural effusion
b. i. Chylothorax
Management entails an e1nergency thoracocentesis to relieve the pressure on the lung
and improve the ventilation. Pleural fluid should be sent for microscopy, culture,
electrolytes, triglycerides, and fat-laden macrophages.
With the history of the broviac line, the most likely diagnosis is a chylothorax associ
ated with insertion of a central line.
)>
:::i
VI
Chylothoraces can also occur due to a congenital malformation of the thoracic duct
� (e.g. in Turner's syndrome) or secondary to trauma (e.g. after cardiac surgery).
�
Management of a chylothorax:
-+,
0
'""I
Insert a chest drain or repeated thoracocentesis.
,-+ Nutritional management is a major concern. An enteral diet rich in medium-chain
::,
(1) triglycerides (MCTs) should be considered for a minimum period of 2 weeks. In
z
(1)
theory, this allmvs the n1ain fat content of the diet to be absorbed directly into the
portal system, rather than being digested, absorbed across the brush border into the
,,
0
enterocyte, reassimilated and entering the lymphatic systen1. An alternative option
3cu is to keep the infant nil orally with total parenteral nutrition containing sufficient
amounts of calories, protein, electrolytes, vitan1ins, etc. to compensate for losses.
,-+
m These infants often develop protein depletion and may require albumin infusions.
>< They niay also be inuTrnnocompromised on the basis of lymphocyte and imnrnno
cu
3 globulin depletion.
Infuse so1natostatin analogue, which may reduce chyle drainage.
When medical management fails, consider surgical ligation of the thoracic duct,
pleurodesis or thoracoabdominal shunting.
Careful counselling of parents regarding this co1nplication is needed and the prob
able need for a prolonged period of intensive care. Mortality rates vary in the lit
erature, but the mi�ority survives.
418
A previously healthy 3-year-old child developed a cough for which she received no
treatment. Ten days later she developed a puffy face and swollen ankles. Her parents
reported a decreased appetite, but good fluid intake, and occasional abdominal pain.
Examination revealed a well-hydrated, normotensive child with facial oedema. Her
abdomen was distended with ascites but non-tender. She had pitting oedema to the
thighs. Urinalysis showed protein ++++ and blood +. Her serum albumin was 3 g/1.
a. What other parameter is characteristically abnormal in this condition?
i. Hb
ii. C3
iii. lgA
iv. Platelets
v. Cholesterol
b. Which renal lesion is the most common cause of this disease in childhood?
i. Focal sclerosis
ii. Minimal change nephropathy
iii. lgA nephropathy
iv. Goodpasture's syndrome
v. Basement membrane disease
c. Which children with this condition need discussion with or referral to a
paediatric nephrologist?
i. Proteinuria > 1 week
ii. Age > 12 years
iii. Hypertension
iv. Serum albumin <2 g/1
v. All children <5 years
419
a. v. Cholesterol
b. ii. Minimal change nephropathy
,0
C c. ii. Age>12years
(I)
VI iii. Hypertension
o·
,-+
:J Nephrotic syndron1e is a clinical condition resulting from the loss of large an10unts of
VI
OJ
protein from the blood into the urine. This is associated with hypoproteinaen1ia,
:J oedema, and hypercholesterolaemia, and lipiduria. Nephrotic-range proteinuria is found
a.
when there is 4+ protein on the urine dipstick, which correlates with proteinuria of
)>
:J
VI
n1ore than 40 mg/kg/day.
The nephrotic syndrome may be a feature of any form of childhood glomerulonephritis
�
VI or may be secondary to other systemic diseases, nephrotoxins or allergic reactions. In
-
0
� approxin1ately 80% of children the aetiology is minimal change nephrotic syndron1e.
,-+ Of these, 60% are between the ages of 1 and 6. Older children are likely to have other
::::r
<D underlying types of glomerulonephritis (i.e. not minimal change) and thus they often
z have a renal biopsy earlier in the course of the disease.
(D
The concentration of plasn1a proteins is also decreased because of increased urinary

"Tl
0 losses, decreased synthesis, or increased catabolism, such as albumin, coagulation inhibi
3
ru
tors and IgG. Sarne plasn1a proteins are, however, increased (possibly because of
,-+ unregulated hepatic production in response to hypoalbuminaemia) such as coagulation
m factors, antifibrinolysins, and most lipoproteins. Cholesterol is also elevated in most
X
ru cases.
3
Children with the following atypical features need discussion with or referral to a
paediatric nephrologist:
• age <1 year or >12 years
• significant haematuria
hypertension
family history
unexplained renal dysfunction
Any children who fail to respond to appropriate treatment with steroids or who have
problems with steroid side-effects also need referral.
420
Benign intracranial hypertension (BIH),
233-4, 325-6
ABO incompatibility, 69-70 Benign Rolandic epilepsy, 35-6
Abscess Biliary atresia, 115-16
amoebic liver, 61-2 Bloch-Sulzberger syndrome, 183-4
brain, 159-60 Bone tumour, 145-6
Acidosis Brain abscess, 159-60
compensated metabolic, 33-4 Bronchogenic cyst, 279-80
fulminant lactic, 329-30 Bronchiectasis, 243-4
Acquired epileptic aphasia, 101-2 Burns, 227-8
Acute lymphoblastic leukaemia, 19-20,
413-14
Acute rheumatic fever, 367-8
Acute transverse myelitis (ATM), Cardiac tamponade, 31-2
89-90 Cat-scratch disease, 267-8
Addison's disease, 133-4, 205-6, 225-6, Cerebral haematoma, 229-30
293-4, 327-8 Cerebral malaria, 387-8
Adrenal gland, androgen-secreting tumour Choking, 279-80
of, 339-40 Chronic bullous disease of childhood,
Adrenarche, premature, 339-40 215-16
Alagille's syndrome, 9-10, 75-6, 107-8, Chronic renal failure, 87-8, 103-4
335-6 Chylothorax, 417-18
Albright hereditary osteodystrophy (AHO), Citrullinaemia, 109-10
67-8 Complex regional pain syndrome (CRPS),
Alcohol ingestion, 361-2 323-4
Alloimmune thrombocytopenic purpura, Congenital adrenal hyperplasia (CAH),
221-2 93-4, 213-14, 311-12, 339-40
Alopecia, 293-4 Congenital central hypoventilation
a-1 antitrypsin deficiency, 75-6 syndrome, 11-12, 223-4
Amoebic liver abscess, 61-2 Congenital complete heart block, 147-8
Ancylostoma braziliense, 181-2 Craniosynostosis, 45-6
Aplasia cutis congenita, 207-8 Crohn's disease, 121-2, 313-14, 405-6
Apnoea, 53-4 Cushing's syndrome, 311-12
Arteriohepatic dysplasia, 9-10, 75-6, 107-8, Cutaneous larva migrans, 181-2
335-6 Cystic adenomatoid malformation of the
Arthritis lung, 315-16
juvenile chronic, 21-2, 229-30 Cystic fibrosis (CF), 71-2, 121-2
juvenile idiopathic GIA), 257-8, 289-90, Cystic hygroma, 357-8
413-4 Cytomegalovirus (CMV), 25-6, 47-8
meningococcal septic, 27-8
Asperger syndrome (AS), 395-6
Ataxia, Friedrich's, 353-4
Autoantibodies, 195-6 Deafoess, sensori-neural, 41-2, 237-8
Autoimmune hepatitis, 201-2 Dehydration, 305-6
Avascular necrosis, 55-6 Dermatomyositis, 79-80
juvenile, 175-6
Developmental problems, 271-2
Diabetes insipidus, 87-8, 111-12, 157-8
Bacterial tracheitis, 375-6 Diabetes mellitus, 87-8, 363-4
Barrter syndrome, 317-18 neonatal, 7-8
Bartone/la henselae, 267-8 Diabetic ketoacidosis, 347-8
Beckwith-Wiedemann syndrome, 131-2, Diaphragmatic hernia, 139-40, 299-300,
277-8 365-6 421
Diarrhoea, toddler's, 121-2 Hepatitis
DiGeorge syndrome, 391-2 autoimmune, 201-2
Dolicocephalic head shape, 45-6 CMV, 47-8
Down's syndrome, 237-8 viral, 287-8
Dyshormonogenesis, 165-6 Hepatitis A, 287-8
Hepatitis B, 73-4, 287-8
Hepatitis C, 91-2
Herpes encephalitis, 51-2, 77-8
Ectodermal dysplasia, 293-4 Herpes simplex virus, 369-70
Electrocardiogram (ECG), 63-4, 137-8, Hib vaccine, 401-2
333-4 Histiocytosis, 231-2
Encephalitis, herpes, 51-2, 77-8 Hurler's syndrome, 261-2
Encephalopathy, 267-8 Hydrocephalus, acute, 295-6
Enterobius vermiwlaris, 151-2 Hydrops fetalis, 357-8
Epilepsy, 101-2 Hymen, 177-8
benign Rolandic, 35-6 Hypernatraemic dehydration, 305-6
Epstein-Barr virus (EBV), 29-30, 247-8 Hyperprostaglandin E syndrome (HPEGS),
317-18
Hypertension
benign intracranial, 233-4, 325-6
Facial nerve palsy, 127-8 prima1y pulmona1y, 245-6, 403-4
Fallots tetralogy, 237-8, 379-80 Hypertensive encephalopathy, 103-4
Fanconi's anaemia, 307-8 Hyperthyroidism, 237-8
Feeding problems, baby, 97-8 Hypoglycaemia, 343-4, 387-8
Fetal heart rate, 153-4, 263-4 Hypokalaemia, 53-4
Feta-maternal haemorrhage, 179-80 Hypomagnesaemia, 161-2
Fibrous dysplasia, 145-6 Hyponatraemia, 49-50
Foramen magnum, mass lesion in, 337-8 Hypoparathyroidism, 225-6, 293-4
Foreign body, 279-80 Hypopituitarism, congenital, 265-6
Fracture Hypotension, 53-4
parietal, 377-8 Hypothyroidism, 237-8
skull, 13-14 acquired, 383-4
midshaft spiral, 17-18 congenital, 165-6
Friedrich's ataxia, 353-4 Hypoxic ischaemic encephalopathy (HIE),
129-30
Galactosaemia, 23-4, 291-2

Gangliosidosis, GM1, 65-6 Immunisations, 359-60, 401-2
Gastric autoimnrnnity, 327-8 Immunosuppressant therapy, 113-14
Gastro-oesophageal reflux, 349-50, 389-90 Impetigo, 169-70
Glycogen storage disease type I, 33-4 Inborn error of metabolism, 83-4
Glycogen storage disease type II, 117-18 Incontinentia pigmenti, 183-4
Goldenhar syndrome, 211-12 Interstitial nephritis, 289-90
Grave's disease, 237-8 Intraventricular blood, 337-8
Growth abnormalities, 277-8 Intussusception, 193-4
Growth hormone deficiency, 95-6 Iron deficiency, 261-2
Haemangioma, hepatic, 163-4 Jaundice, 115-16

Haemolytic anaemia, 411-12 Jones' criteria, 368
Haemolytic uraemic syndrome (HUS), Joubert's syndrome, 297-8
59�60 Juvenile idiopathic arthritis OIA), 257-8,
Haemophilia A, 37-8 289-90, 413-14
Hae111ophil11s iiifluenzae type b, 401-2
Haemorrhage
feta-maternal, 179-80
subdural, 13-14, 377-8 Kartagener's syndrome, 71-2
splenic, 247-8 Kasabach-Merritt syndrome, 171-2
Hashimoto's thyroiditis, 327-8
Hearing loss, sensorineural, 41-2, 237-8
Heart rate, fetal, 153-4, 263-4
Henoch-Schonlein Purpura, 193-4, Landau-Kleffuer syndrome (LKS), 101-2
229-30 Laurence-Moon-Biedl syndrome, 277-8
Leigh syndrome, 297-8
Lennox-Gastaut syndrome, 319-20
Leukaemia, 19-20, 197-8, 351-2, 413-14 Pancytopaenia, 307-8
Lichen sclerosus et atrophicus, 185-6 Pendred syndrome, 41-2
Listeria, 135-6 Pericarditis, 63-4 :J
Liver abscess, 61-2 Periventricular leucomalacia (PVL), 0..
(I)
Lymphoma, 5-6 309-10 X
non-Hodgkins, 81-2 Periventricular parenchymal echodensities,
T-cell lymohoblastic, 81-2 25-6
Pertussis, 199-200
Phagocytic disorder, 385-6
Pimvorms, 151-2
Malaria Plagiocephaly, 345-6
cerebral, 387-8 Plasmodium falciparum malaria, 189-90
Plasmodium falciparum, 189-90 Pleural efft.1sion, 417-18
Maple syrup urine disease, 155-6 Pneumatocoeles, 285-6
Maternal idiopathic thrombocytopenic Pneumocystis carinii, 389-90
purpura, 221-2 Pneumonia, 61-2, 99-100
MCAD deficiency, 141-2, 361-2 Pneumonitis, CMV, 47-8
McArdle's disease, 251-2 Pneumothorax, 331-2
McCune Albright syndrome (MAS), 123-4 Polydipsia, psychogenic, 87-8
Measles, 21-2 Polyglandular autoimmune syndromes,
Meckel's diverticulum, 193-4, 249-50 327-8
Meconium pseudocyst, 255-6 Pompe's disease, 117-18
Medium chain acyl-CoA dehydrogenase Port-wine stain, 173-4, 187-8
(MCAD) deficiency, 141-2, 361-2 Porencephalic cyst, 235-6
Melanocytic naevus, 187-8 Post-haemorrhagic ventricular dilation,
Meningitis, 119-20, 393-4 273-4
neonatal, 295-6 Prader-Willi syndrome, 277-8, 303-4
tuberculous, 409-10 Premature adrenarche, 339-40
Meningococcal disease, 119-20 Primary ciliary dyskinesia (PCD), 71-2
Meningococcal septicaemia, 283-4 Primary pulmonary hypertension, 245-6,
Meningococcal septic arthritis, 27-8 403-4
Methaemoglobinaemia, 281-2 Prolonged QT syndrome, 137-8
Micrognathia, 39-40 Pseudopseudohypoparathyroidisn1, 67-8
Miliary tuberculosis (TB), 5-6 Pseudotumour cerebri, 233-4, 325-6
Mitral stenosis, 389-90 Pulmona1y haemosiderosis, 373-4
Myelitis, 267-8 Pyoderma gangrenosum, 203-4
Myotonic dystrophy (MD), 355-6 Pyruvate dehydrogenase deficiency, 33-4
Naevus flammeus, 173-4 QT interval, 137-8, 333-4

Necrotising enterocolitis (NEC), 3-4
Neonatal alloimmune thrombocytopenia
(NAIT), 221-2
Nephritis, interstitial, 289-90 Reflex sympathetic dystrophy (RSD),
Nephrotic syndrome, 275-6, 289-90, 323-4
419-20 Renal failure
Neuroblastoma, 231-2 chronic, 87-8, 103-4
Neuronal migration disorder, 297-8 end-stage, 149-50
Neutrophil disorder, 385-6 Rheumatic fever, 229-30, 367-8
Nieman-Pick disease, 65-6 Rickets, 397-8
Non-accidental injury (NAI), 241-2 Right atrial hypertrophy, 117-18
Non-ketotic hyperglycinaemia, 343-4 Rolandic epilepsy, benign, 35-6
Noonan syndrome, 105-6
Salmonella infection, 193-4

Obliterative bronchiolitis (OB), 113-14 Sarcoidosis, 351-2
Ondine's curse, 11-12, 223-4 Scarlet fever, 21-2
Organic acid disorders, 33-4, 361-2 Schwachmann-Diamond syndrome, 71-2
Osteomyelitis, 231-2 Schwachmann's syndrome, 371-2
Ovaries, androgen-secreting tumour of, Scoliosis, 237-8
339-40 Screening tests, 415-16
Sensorineural hearing loss, 41-2, 237-8 Tourette's syndrome, 143-4
Sepsis, 371-2 Toxic shock syndrome, 227-8
CNlV, 47-8 Tracheitis, bacterial, 375-6
neonatal, 369-70 Transposition of the great arteries (TGA),
::J Sexual abuse, 185-6 53-4, 245-6, 379-80
0..
(I)
Shaken baby syndrome, 209-10 Tr;msverse myelitis, 89-90
Sjogren's syndrome, 147-8 Tuberculosis, 351-2
Smith-Lemil-Opitz syndrome, 39-40 miliary, 5-6
Soto's syndrome, 277-8 Tuberculous meningitis (TBM), 409-10
Space occupying lesion, 393-4 Tuberous sclerosis complex, 15-16
Spinal muscular atrophy (SIVlA) type 2, Turner syndrome, 321-2
57-8
Splenic haemorrhage, 247-8
Staphylococcal scalded skin syndrome,
169-70 Urea cycle disorder, 109-10, 399-400
Stevens-Johnson syndrome, 197-8
Still's disease, 21-2
Strawberry naevus, 187-8
Streptococcal infection, 197-8 Vaccinations, 359-60, 401-2
Subdural haemorrhage, 13-14, 377-8 Ventricular tap, 274
Surfactant deficient lung disease, 47-8 Ventriculitis, 295-6
Survival motor neurone (SMN) Vitamin deficiency, 9-10
gene-testing, 57-8 Vitamin D deficiency, 241-2, 397-8
Swimming pools, 239-40 Vitamin K deficiency, 75-6, 241-2
Sydenham's chorea, 367-8
Systemic lupus erythematosus (SLE), 195-6
West's syndrome, 235-6

Whooping cough, 199-200
Tay-Sach's disease, 65-6 Wilm's tumour, 131-2
T-cell lymphoblastic lymphoma, 81-2 Wilson's disease, 201-2
Tension pnemnothorax, 331-2 Wolff-Parkinson-White (WPW) syndrome,
Threadworms, 151-2 407-8
Thrombocytopenic purpura, 221-2
Toddler's diarrhoea, 121-2
Todd's palsy, 347-8
Total anomalous pulmonary venous drainage Zellweger syndrome, 219-20
(TAPVD), 269-70, 379-80 Zinc deficiency, 191-2
424

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MRCPCH Part 2:

Questions and Answers for the

Kate H. Creese MB Bch ocH DRcoc MRCPCH

Colin V.E. Powell MBchB ocH MRCP FRACP FRCPCH MD

Patrick H.T. Cartlidge DM FRCP FRcPcH

CHURCHILL LIVINGSTONE An imprint of Elsevier Limited

© 2008, Elsevier Limited. All rights reserved.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in

First published 2008

British Library Cataloguing in Publication Data

Library of Congress Cataloging in Publication Data

Working together to grow

Chapter 2 Case 2.1 Case 2.20 43

Chapter 3 Case 3.1 - Case 3.19 85

Chapter 4 Case 4.1 - Case 4.20 125

Chapter 5 Case 5.1 Case 5.24 167

Chapter 6 Case 6.1 - Case 6.20 217

Chapter 7 Case 7.1 - Case 7.20 259

Chapter 8 Case 8.1 - Case 8.19 301

Chapter 9 Case 9.1 - Case 9.19 341

Chapter 10 Case 10.1 - Case 10.19 381

Q TB can be suspected with a positive Mantoux/Heaf test in the absence of BCG

3 therapy was cornrnenced.

� Following confirmation of the diagnosis, an experienced paediatric otolaryngologist

16 *A definitive diagnosis of TSC requires t,vo of these major features.

An infant born at 33 weeks' gestation with a birthweight of 1596 g (3 rd-10th centile)

What is the most likely diagnosis?

D Differential diagnosis should include cardiac tamponade, septicaemia, congenital heart

� iv. Plasma ammonia

3 15 units/kg of factor VIII.

c. What syndrome is he most likely to have?

Tympanogram: BONE CONDUCTION

� L y,:_ vz_ Masked right [ Masked left ]

Congenital causes of sensori-neural hearing loss

Acquired causes of sensorineural deafness

Congenital CMV infection affects approximately l% of newborn infants, although n1ost

Fig 2.6.A Fig 2.6.B

An 8-year-old, previously healthy boy, presented with a 6 h history of fever, irritability

D With evidence of acute haemolysis, thrombocytopenia and deteriorating renal function,

Second-line investigations Indications Comment

Blood ammonia Encephalopathy Normal <80 �1mol/l

Blood lactate Encephalopathy, acidosis Normal <2.5 mmol/1

Insulin, (-peptide, growth Hypoglycaemia Endogenous hyperinsulinisrn

Urinary reducing substances Liver/renal disease Unreliable for diagnosis of galactosaemia

Urinary/plasma amino acids Encephalopathy, hypoglycaemia, Aminoacidopathies, urea cycle defects

Time (�ins) Glucose (mmol/1) GH (mU/1) Cortisol (nmol/1)

90 3.3 4.0 141

180 4.6 3.2 115

,What is the likely cause of his raised blood pressure?

A 5-year-old girl with CF underwent a heart-lung transplant. At the regular review in

His blood tests on day 20 were as follows:

Ca P04 ALP TRP TmP04' Peak LH Peak FSH Oestradiol

2.43 0.92 1406 87% 0.8 10.9 7.2 78

What is the likely diagnosis?

a.. line treatn1ent. Recurrence despite adequate treatn1ent is con1mon.

3 Primary nephrogenic diabetes insipidus is usually inherited as an X-linked recessive

20 minute uptake � 31%

Fig 5.1.A Fig 5.1.B

A newborn baby presented at birth with the skin lesion shown.

3 sorne recovery of developn1ental skills between episodes of regression or a slowly pro

Q Acanthosis nigricans is asymptomatic, brown-black, with a velvety texture. Peduncu