Expanded Newborn Screening CASE REPORT

ORIGINAL ARTICLE

Enhancing HeartCase Failure and Short

Detection StatureInherited
of Selected in a 43 year-old
Disordersmalethrough
Expanded
Katerina T. leyritana 1 Newborn
, Ma. Czarlota Screening1, Amado
M. Acelajado-Valdenor in theo.Philippines
Tandoc III2 and Agnes D. Mejia1
1
Department of Medicine, College of Medicine and Philippine General Hospital, University of the Philippines Manila
Department of Pathology,Carmencita D. Padilla *1,2
2
College of Medicine, University of the Philippines Manila
*Tomas B. Aguirre Professorial Chair in Pediatrics

1Department of Pediatrics, College of Medicine and Philippine General Hospital, University of the Philippines Manila
2Newborn Screening Reference Center, National Institutes of Health, University of the Philippines Manila

Presentation of the case require regular laxative use. There was also a report of two
This is a case of a 43-year-old male presenting with short more syncopal episodes. He was brought to another doctor
stature and heart failure. The patient was admitted at the in a private hospital where the assessment was still a “heart
medicine ward of the Philippine General Hospital (PGH) problem”. The patient was again prescribed unrecalled
for dyspnea. This paper will investigate several issues: medications and again was lost to follow-up. This time,
differentiating congenital from acquired hypothyroidism, however, symptoms were persistent. He later consulted at
the relationship between hypothyroidism and the another local hospital, where he was admitted and managed
cardiomyopathies, and the therapeutic options in patients as a case of anemia and bronchial asthma. He was discharged
with cardiomyopathy secondary to hypothyroidism. slightly improved after four days, only to have recurrent heart
The patient had been born full term to a then 31-year- failure symptoms, prompting admission at PGH.
old Gravida 4 Para 3 (G4P3), the 4th of 9 siblings, with an Upon admission the patient was in mild respiratory
apparently unremarkable delivery at home facilitated by distress, with stable vital signs and no note of fever. Pertinent
a traditional birth attendant. He was noted to be normal physical exam findings included Introductionshort stature, thick lips, non-
at birth. The patient was allegedly at par with age both pitting periorbital edema, dry
Newborn screening (NBS)skin,isa displaced apical impulse,
a public health activity
physically and mentally until eight years old when he was crackles on both lung fields, and bilateral non-pitting bipedal
aimed at the early identification of infants who are affected
said to have stopped growing in height. He was brought to edema.
by certainTheregenetic/metabolic/infectious
was also a 3 cm x 3 cm reducible conditions.umbilical
Early
a private doctor, whose diagnosis was undisclosed, and he hernia. However,
identification thereconditions
of these was no pallor, no neckimportant,
is crucially vein distention,
since
was given medications to increase height, which the patient no apparent
timely congenitalleads
intervention malformations,
to significant no cardiac murmurs
reduction of
took for only one month with no improvement. Through the and no clubbing.
morbidity, Thereand
mortality, wasassociated
also no note of an anterior
disabilities neck
in affected
years, the patient was apparently well, although still of short mass.
newborns.1 Newborn screening for phenylketonuria (PKU),
stature, with thick lips, coarse facial features and dry skin. laboratory
using workup
a bacterial showed cardiomegaly
inhibition assay developed with pulmonary
by Robert
He was notably slow in ambulation. He was said to have congestion,
Guthrie in thoracic
the earlydextroscoliosis,
1960s usingand atheromatous
blood absorbed aorta
ontobya
bronchial asthma at age 15 years, and since then he had been chest
specialradiograph,
filter paper,and setleft
theventricular
framework hypertrophy by 12-lead
for NBS.2 Successful
taking salbutamol tablets occasionally for bouts of dyspnea electrocardiogram
newborn screening(12-l for PKUECG)and (Figures
improved1 andmicro
2), normocytic
detection
occurring one to two times annually. normochromic anemia
techniques for other (Hgb 90 led
conditions mg/dl),
to the dyslipidemia,
gradual inclusion and
The patient’s symptoms started in 2001 when he was pre-renal
of other azotemia
disorders (serumin NBS creatinine 123 mmol).
programs over Electrolytes
the years.
reported to have sudden loss of consciousness. During this on admission
Presently, both showed
developed slight
and hyponatremia,
developing countries hypokalemia,
include
time, the patient did not have any symptoms of heart failure; and hypochloremia
newborn screening (serum Na 136, Kof3.35,
as a standard careClcovering
86). Blood a gases
wide
no prior seizures, cyanotic episodes, chest pain, headache, or revealed partially compensated
range of conditions – endocrinology, metabolic alkalosis
metabolic, with mild
hematologic,
blurring of vision. He regained consciousness shortly after and hypoxemia.
immunologic, The patient was
infectious, andnoted
many to others.
be hypothyroid based
3 This includes

was brought to a private physician, whose assessment was a on

the elevated
national serum
newborn thyroid-stimulating
screening program hormone (TSH) and
in the Philippines.
“heart problem”. He was prescribed unrecalled medications markedly
The main decreased
goal of newbornserum screening
free thyroxine is to (FT4).
detect The
and exact
treat
taken for a few months and eventually discontinued when values are shown
asymptomatic in Tables
heritable 1 and 2.early in order to decrease
disorders
the syncopal episode did not recur. Upon morbidity
related admission to andthe mortality.
wards, the4 patient was managed
Multiplex newborn
_______________
In the next four years, the patient would develop as having assays
congestive heart failure from cardiomyopathy
screening for the hemoglobinopathies developed in
intermittent,
Presented at the progressive exertional
10th Newborn Screening dyspneaOct.and
Convention, bipedal
2, 2012, SMX secondary
the 1980s and to acquired
metabolic hypothyroidism.
disorders developed oral loop diuretics,
in the 1990s
edema. later
Convention onPasay
Center, thisCity.
would be accompanied by generalized angiotensin-converting
have led to significant enzyme additions(ACE) inhibitors,
to newborn beta-
screening
body weakness, anorexia, and constipation, severe enough to blockers,
panels in statins, and levothyroxine
recent years. The extent towere whichstarted.
theseElectrolyte
particular
Corresponding author: Carmencita D. Padilla, MD
Newborn Screening Reference Center correction was Philippine
disorders affect instituted. newborns
The sectionsis notof Endocrinology
known; however,
National Institutes of Health and Cardiovascular
clinical case data inDiseases were co-managing
the Philippines and data on the Filipino
patient
Corresponding author: Ma. Czarlota Acelajado-Valdenor, M.D.
University of the Philippines Manila
Department of Ermita,
Medicine together
newbornswith in the General provide
California Medicineincidence
service. data useful in
625 Pedro Gil St, Manila, Philippines
Philippine General Hospital He soon
assessing developed
probable respiratory
incidences of thefailure, upon which the
hemoglobinopathies
Telephone: +632 5224396
Taft Avenue,
Email: Manila, 1000 Philippines
[email protected] considerations were acute
(i.e. thalassemias) and pulmonary
other metabolic congestion, nosocomial
conditions (i.e.
Telephone: +632 554-8488 pneumonia, to rule out an acute coronary event. He was later
Email: [email protected]

12 ACTA MEDICA
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PHIlIPPINA Vol. 47
VOL. 46 NO. 4 2012 - VOL. 43 NO.
N0. 41 2009
2013
 Heart Failure and Expanded
Short StatureNewborn
in a 43 year-old male
Screening

Table 1. acid
organic Initial
andlaboratory
fatty acid Results
oxidation disorders) not currently Table 1. Milestones of the Newborn Screening Program in
part of the Philippine newborn screening panel. the Philippines
CBC Blood chem. Urinalysis ABG
Reference Result Reference Result Color straw pH 7.408
Newborn Screening in the Philippines Year Milestone
Value Value 1996 Pilot screening initiated for CH, CAH, GAL, PKU,
WBC Formalized5-10
NBS in the Philippines
4.5
began in June 3.9-6.1
RBS 1996, 6.3 Transp Clear pCo2 49.1
homocystinuria (HCY).
and
RBC was integrated
4-6 into the public health delivery
HGBA1C system
4.27-6.07 6.4
1998 Sp Gravity
Pilot screening initiated for1.010
G6PD deficiency. po2 70
HGB years later
eight with enactment
120-150 BUN Act 9288,2.6-6.4
90 of Republic also 5.0
1999 pH
HCY discontinued (no cases8.0
detected) and HCo3
replaced with31.3
G6PD
HCT as the0.38-0.48
known Newborn Screening 0.27 CREA
Act of 53-115
2004. A National 123 Sugar (shown toNEG
deficiency o2 sat in the pilot
have high incidence 93.6
MCV 80-100 Fl AlB 34-50 32 Protein
study). NEG Fio2 21%
Comprehensive Newborn Screening System (NCNBSS) was
MCH 27-31 PG TAG 0.34-1.7 0.82
2000 Screening RBC
program evaluated 0-1for cost effectiveness
Temp 36.9
and policy
established
MCHC under
320-360RA G/l9288 to ensure thatHDl every baby born in
0.91-1.56 0.67 WBC recommended.
changes 0-2
the
RDW Philippines is
11.5-15.5% offered the opportunity
lDl to undergo
1.1-3.8 2004
4.21 Newborn Screening
Cast PBS
Act of 2004 enacted and the Implementing
PlT ToTAl Rules
Epithand
cell Regulations completed.
newborn 200-400 and thusIncbe spared
screening fromCHol 4.2-5.2
the adverse 5.25 Rare Slight poikilocytosis,
2005 NBS included in the licensing requirement of hospitals.
outcomes of a limited number of heritable conditions15-37
RETIC 0.005-0.015 AST that 95
2006
Bacteria occ’l acanthocytes,
NBS included in the Philippine Health Insurance ovalocytes,
Corporation
SEG 50-70% 48 AlT 30-65 91 Mucus th Rare slight
can result in mental retardation and death if left undetected (PHIC) newborn package, covering 90%toxic granulation,
of the NBS fee.
lYMPH 20-44% 50 Alk po4 184 Crystals Rare slight anisocytosis
2011 PHIC newborn package expanded to cover 100% of the NBS fee.
and untreated.2-9% By the end of 2 2011, newborn screening140-148
was
4,5
MoNo NA 136.9 Am urates
2012 Maple Syrup Urine Disease (MSUD) added to Philippine NBS
being
Eo offered0-4% to 42% of the Philippine
0 newborn
K population.
3.6-5.2 3.35
panel.
BASo
The 0-2% of Health0 (DOH) and
Department Cl other program 100-108 86
BlAST 0% 0 CA++ 2.12-2.52 2.37
implementers have been, and continue to be, aggressive in Expanded Newborn Screening
P 2.27
identifying strategies that have intensified MG++ newborn
0.74-1 0.83
In recent years, multiplex screening for
screening awareness in communities and increased hemoglobinopathies using electrophoresis, isoelectric
screening coverage for home deliveries, which account for focusing, and/or high performance liquid chromatography
60% of the newborn population.6 (HPLC), and for the amino acids, organic acids and
fat pad. Cardiac enzymes were not consistent with an acute
TableAs2. of December
Thyroid 2012,Tests
Function six disorders are included in the acylcarnitines using tandem mass spectrometry (MS/MS)
NCNBSS. The incidences of the screened disorders are: coronary event (Table 3), however, intravenous (IV) heparin
Reference Value Result tremendouslywith
(overlapping increased the number
oral warfarin) wasofstill
detectable
given toconditions
cover for
congenital
Free T4 hypothyroidism (CH) 1:3,004; congenital
(0.8-2.0) 0.02 ng/dladrenal in newborn screening. 7,8,9,10 While hemoglobinopathy
hyperplasia (CAH) (0.4-6.0)
1:10,604; phenylketonuria the presence of a possible lV thrombus as demonstrated
TSH 24.75 Uiu/ml (PKU) newborn screening
1:388,367; galactosemia (GAL) 1:310,694 and glucose-6- by rheologic stasis has
on generally been limitedMedications
cardiac ultrasound. to the US,
expanded screening by MS/MS has been
were shifted to IV diuretics and inotropes; oral digoxin reported to vastly
was
phosphate dehydrogenase (G6PD) deficiency 1:50. Maple improve the outcomes from newborn screening in many
syrup urine disease (MSUD) was added to the screening started. IV antibiotics were given for possible pulmonary
countries The
infection. including
patient laterAustralia,
on showed Europeimprovement, and and North
was
panel in the last quarter of 2012 and incidence data is not yet America. 11,12,13 Screening by MS/MS has approximately
eventually weaned off from ventilatory support, extubated,
available.6 doubled the detection rate of metabolic disorders compared
Samples are being collected from over 4,000 newborn to that achieved by conventional methods.7 For some
screening facilities (NSFs) nationwide (including birthing Table 3. Cardiac Enzymes
disorders (e.g. fatty acid oxidation disorders, MCAD
centers, lying-in centers, rural health units, infirmaries, deficiency) the detectionReference Range
rate (mmoL)
is significantlyResulthigher by
secondary/tertiary hospitals). NSFs offer NBS as part of Qualitativethan by clinical diagnosis.11,14,15,16 PoSITIVE
screening
DOH and Philippine Health Insurance Corporation (PHIC) Troponin
SinceI neither hemoglobinopathy screening nor
licensing requirements for hospital accreditation. These CK-MB 0-6.0 1.14
expanded
CK-ToTAlmetabolic screening 21-232 are currently a543part of the
facilities assist the newborn screening effort by educating Philippine newborn screening program, questions exist as to
parents about NBS during prenatal classes, collecting blood whether their inclusion could and should be adopted. Is it
samples for NBS, sending samples to Newborn Screening worthwhile to expand the Philippine NBS Program? How
Centers (NSCs), recalling patients found to be at increased many additional cases can be detected if this is done? While
risk through the screening process, and assisting in the these questions could be the focus of a research project
Figure
referral1.ofElectrocardiogram
screen positive patientsupon admission
for proper management. involving pilot screening, such a project would be costly and
Four Newborn Screening Centers (NSCs) currently provide time consuming. A more efficient and equally effective
laboratory and follow-up services for more than 4,000 NSFs. method for answering these questions exists. Data from a
transferred to the intensive care unit (ICU) for ventilatory
The NSCs are strategically located to provide newborn
support and closer monitoring. on bedside cardiac ultrasound, large population of Filipino newborns in another well-
regional screening services — NSC-National Institutes of
there was a finding of eccentric left ventricular hypertrophy, established, high quality screening program, such as
Health in Manila; NSC-Visayas in Iloilo City; NSC-
global hypokinesia with depressed overall systolic function California, can be analyzed and extrapolated to the
Mindanao in Davao City; and NSC-Central Luzon in
with concomitant spontaneous echo contrast on left ventricular Philippine newborn population. The CNSP provides a
Angeles City.6
(lV) cavity suggestive of rheologic stasis, the ejection fraction source for this information. This report analyzes data on
was A25%,summation
with moderate of mitral
the major activities
regurgitation, and
moderate Filipino newborns screened through the CNSP and
accomplishments of the NCNSP across time are
aortic regurgitation with aortic sclerosis, severe tricuspid presented in extrapolates case detection data to the Philippine newborn
Table 1.
regurgitation with mild pulmonary hypertension, pulmonary population (assuming full coverage of the 2 million
regurgitation, and minimal pericardial effusion or pericardial Figure
newborns 2. Chest
born radiograph
each year). on admission

Vol. 46
VOL. 43 NO.
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2012 - VOL. 47 NO. 1 2013 ACTA MEDICA
ACTA MEDICA PHILIPPINA
PHIlIPPINA 25
13
Expanded Newborn Screening CASE REPORT

Heart Method Failure and Short Stature in aOf43these,

ethnicities. year-old111,127 male were Filipinos and 199 had
Screening data for Filipino newborns born between 7 confirmed diagnoses for screened disorders. Table 2 gives a
Katerina
July 2005 and 6 T. Julyleyritana , Ma. Czarlota
2011 in California,
1
M. Acelajado-Valdenor
USA included in the breakdown 1
, Amado of o. Tandoc III
diagnoses and Agnes
among
2
D. Mejia
the Filipino patients
1

California Genetic Disease Screening Program database were confirmed with a disorder. Table 3 presents the ethnicity of
obtained and analyzed.
1
DepartmentAs of Medicine, College of Medicine
a requirement of the and Philippinethe
CNSP, General Hospital,
parents University
of the newborns.of the Philippines Manila the metabolic
Table 4 presents
blood specimens were collected
2
Department
on allof newborns
Pathology, College of Medicine,
by heel- and University
hemoglobinof the Philippines
disorders Manila in Filipino newborns – the
stick between 12 hours and 6 days after birth, with most numbers picked up by the CNSP and extrapolated to annual
specimens collected between 12 and 72 hours of age. number of cases assuming a 100% coverage for the 2 million
Following collection, specimens were sent by the collecting annual births.
hospitals to one of seven state-approved laboratories for
testing. Screening for metabolic disorders was conducted Table 2. Diagnosis of confirmed cases in the Filipino
using MS/MS to measure Presentation of the case of acylcarnitines,
concentrations require
newbornregular laxative
population use. There was also a report of two
in CNSP
This isacids
organic a case and
of a 43-year-old
amino acids. male Endocrine
presenting with short
disorders more syncopal episodes. He was brought to another doctor
stature andcongenital
[including heart failure. The patient was
hypothyroidism (CH)admitted at the
and congenital in aTypeprivate hospital where
of Disorder Number the assessment
Percentage ofwas Percentage
still a “heart
of
of Cases Cases among Cases among
medicinehyperplasia
adrenal ward of the Philippine
(CAH)] were General
screenedHospital (PGH)
by fluorescent problem”. The patient was again prescribed unrecalled
Filipinos with Filipino
for dyspnea. This
immunoassays, similarpaper
to the will investigate
procedure several
currently issues:
in place in medications and again was lost Confirmed to follow-up. Population
This time,
differentiating
the Philippines.congenital
Additional from acquired
screening for hypothyroidism,
CAH included however, symptoms were persistent. He later consulted
Diagnosis Screened at
the relationship
second-tier testing by between hypothyroidism coupled
liquid chromatography and the to another local hospital, where he wasN=admitted 199 and
N=managed
111 127
Endocrine Disorders 51 26.6% 0.05%
cardiomyopathies,
MS/MS for and the therapeutic
androstenedione, options in
cortisol, and patients
17- as a case of anemia and bronchial asthma. He was discharged
Hemoglobinopathies 109 54.8% 0.10%
with cardiomyopathy secondary
hydroxyprogesterone. Hemoglobin to hypothyroidism.
disorders were screened slightly
Amino acid improved
disordersafter four6days, only3.0% to have recurrent 0.01%heart
TheHPLC.
using patientGalactosemia
had been born andfull term to adeficiency
biotinidase then 31-year-(BD) failure
Organicsymptoms,
acid disordersprompting 7 admission 3.5% at PGH. 0.01%
old Gravida
were screened 4 Para with3 (G4P3), the 4th of
fluorometric 9 siblings,
enzyme with for
assays an Upon
Fatty admission the 10
acid disorders patient was5.0% in mild respiratory
0.01%
Other disorders 16 8.0% 0.01%
apparently unremarkable
galactose-1-phosphate uridyldelivery at home
transferase andfacilitated
biotinidase by distress,
Total
with stable vital signs 199
and no note of fever.~0.18%
~100.0%
Pertinent
a traditional
activity, birth attendant.
respectively. CF wasHe was noted
screened usingto abefour-step
normal physical exam findings included short stature, thick lips, non-
at birth. The
approach patient was allegedly
(immunoreactive trypsinogen at parfollowed
with ageby both a pitting periorbital edema, dry skin, a displaced apical impulse,
Table 3. Parental ethnicity of Filipino newborns with
physically DNA
selected and mentally
mutation until panel,
eight years old when
followed by heDNA was crackles on both lung fields, and bilateral non-pitting bipedal
confirmed diagnosis in CNSPa
said to have ifstopped
sequencing, growing
the mutation panelin height.
identifiedHe was
two brought
mutations, to edema. There was also a 3 cm x 3 cm reducible umbilical
a private
and a sweatdoctor,
test).whose diagnosis
Screening for CF wasand undisclosed,
BD startedand on he16 hernia. However, there was no pallor,No. noofneck vein distention,
Filipino
was given
June 2007 medications
and thus, the to data
increase height,forwhich
reported thesethe patient
disorders no apparent congenital malformations, No. of no with
patients cardiac murmurs
Ethnicity Percentage
took for onlyonly
represented one amonth
3-yearwith no improvement.
interval. 17 Through the and no clubbing. There was also no note
Filipinos of an anterior neck
Confirmed
Diagnosis
years, the patient was
Information on apparently
race/ethnicity well, of
although still of short
the infants was mass.
Filipinos only 61,088 101 55.0%
stature, with
reported by thethickmother,
lips, coarse
who facial features and
was instructed dry skin.
to select all laboratory
Filipino + White workup showed cardiomegaly
18,546 26 with pulmonary 17.0%
He was notably
applicable choicesslow from
in ambulation.
a selection He was of said
18 to have
distinct congestion, thoracic dextroscoliosis,
Filipino+ Hispanic 8.507 and atheromatous
13 aorta
7.6%by
bronchial asthma
racial/ethnicity at age 15on
categories years,
the NBSand test
since then he had
requisition been
form. 17 chest radiograph,
Filipino+ and left ventricular
Hispanic + White 3,849 hypertrophy
6 by 12-lead
3.4%
Other Filipinos 19,127 53 17.0%
takingAllsalbutamol
positive test tablets
results occasionally
were reported for bouts
to theofCalifornia
dyspnea electrocardiogram (12-l ECG) (Figures 1 and 2), normocytic
All Filipinos 111,127 199 100.0%
occurring
Genetic one toScreening
Disease two timesProgramannually.(GDSP) through a secure normochromic
a
personal communication anemiawith (Hgb 90 mg/dl),
Lisa Feuchtbaum, DrPH,dyslipidemia, and
MPH, Genetic Disease
The patient’s symptoms
computer-based online Screening started inInformation
2001 when System.he was pre-renal azotemia
Screening Program, (serum
California creatinine
Department 123
of Public mmol).
Health, Electrolytes
Richmond, California,
reported towith
Newborns haveinitial
sudden loss of consciousness.
screen-positive results wereDuring this
referred on
USA,admission
August 2012. showed slight hyponatremia, hypokalemia,

time,a thestate-contracted
to patient did not have any symptoms
specialty follow-up of heart
centerfailure;
for and hypochloremia (serum Na 136, K 3.35, Cl 86). Blood gases
no prior seizures, cyanotic episodes, chest pain, headache, or revealed partially compensated Discussion metabolic alkalosis with mild
endocrine, metabolic, hemoglobin, or CF disorders. Center
blurring of vision. He regained consciousness shortly after and Multiplex
hypoxemia. The newborn
patient was noted screening
to be hypothyroid tests based for
specialists determined whether referred children had a
was brought to a private physician, whose assessment hemoglobinopathies in the 1980s
on elevated serum thyroid-stimulating hormone (TSH) and and metabolic
testing. 17 was a
8
disorder through appropriate confirmatory
“heart problem”. He was prescribed unrecalled medications conditions decreased
markedly in the 1990s 18 have led to decreased morbidity
serum free thyroxine (FT4). The exact
Data on the final diagnosis and ethnicity of the parents
taken for a few months and eventually discontinued when and mortality
values are shown ininnewborn
Tables 1 and screening
2. programs adopting
were collected from the database. The percentage of patients
the syncopal episode did not recur. these Upon admission to the wards, the patient was including
techniques. Expanded newborn screening managed
with the disorder was reported out of the total Filipino
In the next four years, the patient would develop as having congestiveand
hemoglobinopathies heartmetabolic
failure from conditions detected
cardiomyopathy
children screened and according to the ethnicity of the
intermittent, progressive exertional dyspnea and bipedal through multiplex assays has become
secondary to acquired hypothyroidism. oral loop diuretics, newborn screening
parents.
edema. later on this would be accompanied by generalized standard-of-care acrossenzyme
angiotensin-converting the globe (ACE) including:
inhibitors, Northbeta-
Extrapolations to the current Filipino newborn
body weakness, anorexia, and constipation, severe enough to blockers, statins, and levothyroxine were started. Electrolyte
America, 13 Europe,12,19 Latin America, 20 and Asia and the
population in Philippines relied on birth statistics using an
correction
Pacific.21-26 was instituted. The sections of Endocrinology
annual birth of 2 million (www.doh.gov.ph).
and Based
Cardiovascular
on clinicalDiseases were co-managing
case detection, there are a the patient
substantial
Corresponding author: Ma. Czarlota Acelajado-Valdenor, M.D.
Department of Medicine together with the General Medicine service.
number of Filipino patients with hemoglobinopathies. There
Results
Philippine General Hospital are He soon developed respiratory failure, upon which the
400 patients registered in the Thalassemia Center of the
From 7 July 2005 to 6 July 2011, there were 3,460,839
Taft Avenue, Manila, 1000 Philippines considerations
Philippines in were
Quezon acute pulmonary
City congestion,
and 30 patients nosocomial
registered with
newborns +632
Telephone: screened
554-8488in the CNSP including various races and
pneumonia,
the Mindanao to rule out an acuteGroup.
Thalassemia coronaryPublished
event. He wasdatalater on
Email: [email protected]

12 ACTA MEDICA
26 ACTA MEDICA PHILIPPINA
PHIlIPPINA Vol. 47
VOL. 46 NO. 4 2012 - VOL. 43 NO.
N0. 41 2009
2013
 Heart Failure and Expanded
Short StatureNewborn
in a 43 year-old male
Screening

Table 1. Initial laboratory Results

Table 4. Metabolic and hemoglobin disorders in Filipino newborns: Data from the CNSP extrapolated to Philippine
newborns CBC Blood chem. Urinalysis ABG
Reference Result Reference Result Color straw pH 7.408
Number of Cases Expected Annual Number of
Value Conditions Value Prevalence
in CNSP Cases in the Philippinesa
WBC 5-10 4.5 RBS 3.9-6.1 6.3 Transp Clear pCo2 49.1
Hemoglobinopathies
RBC 4-6
α-thalassemia major
HGBA1C 4.27-6.07 6.4 5 Sp Gravity
1:22,225
1.010 po2100 70
HGB 120-150
β-thalassemia major 90 BUN 2.6-6.4 5.0 1 pH1:111,127 8.0 HCo320 31.3
HCT 0.38-0.48
Hb E/Beta + thalassemia 0.27 CREA 53-115 123 1 Sugar
1:111,127 NEG o2 sat20 93.6
MCV
Hb H disease 80-100 Fl AlB 34-50 32 93 Protein1:1,195 NEG Fio21860 21%
MCH
Hb H/ Constant27-31 PGdisease
Spring TAG 0.34-1.7 0.82 2 RBC1:55,564 0-1 Temp40 36.9
MCHC
Hb Variant/Beta 320-360 G/l
+ thalassemia HDl 0.91-1.56 0.67 1 WBC 1:111,127 0-2 20
RDW
Homozygous EE 11.5-15.5% lDl 1.1-3.8 4.21 3 Cast1:37,042 60 PBS
PlT
Sickle C disease200-400
(Hb S/C disease) Inc ToTAl CHol 4.2-5.2 5.25 2 Epith cell
1:55,564 Rare Slight 40
poikilocytosis,
RETIC 0.005-0.015
Sickle cell anemia (Hb S/S disease) AST 15-37 95 1 Bacteria
1:111,127 occ’l 20
acanthocytes, ovalocytes,
SEG 50-70% 48 AlT 30-65 Acid Disorders
Amino 91 Mucus th Rare slight toxic granulation,
lYMPH
Phenylketonuria (PKU)
20-44% 50 Alk po4 184 4 Crystals
1:27,782 Rare 80
slight anisocytosis
Variant hyperphenylalaninemia
MoNo 2-9% 2 NA 140-148 136.9 1 1:111,127
Am urates 20
Maple syrup urine disease (MSUD)
Eo K 3.6-5.2 3.35 1 1:111,127 20
0-4% 0
Organic Acid Disorders
BASo 0-2% 0 Cl 100-108 86
Methylmalonic acidemia - MMA - (mut 0) 3 1:37,042 60
BlAST 0% 0 CA++ 2.12-2.52 2.37
Methylmalonic acidemia - MMA (mut –) 2 1:55,564 40
P 2.27
β-ketothiolase deficiency (BKT) 1 1:111,127 20
MG++ 0.74-1 0.83
Isobutyryl-CoA dehydrogenase deficiency (IBDHD) 1 1:111,127 20
Fatty Acid Oxidation Disorders
Medium chain acyl-CoA dehydrogenase deficiency (MCAD deficiency) 2 1:55,564 40
Short chain acyl-CoA dehydrogenase deficiency (SCAD deficiency) 3 1:37,042 60
Very long chain acyl-CoA dehydrogenase deficiency (VLCAD deficiency) fat pad.3 Cardiac enzymes
1:37,042were not consistent
60 with an acute
Table 2. Thyroid Function Tests
Other fatty acid oxidation disorder coronary 2 event (Table 3), however, intravenous
1:55,564 40 (IV) heparin
Reference Value Result Others
(overlapping with oral warfarin) was still given to cover for
Partial
Free T4BD deficiency (0.8-2.0) 0.02 ng/dl 1 1:111,127 20
CFTR-Related Metabolic Syndrome the presence of a possible
1:22,225 lV thrombus as 100demonstrated
TSH (0.4-6.0)(CRMS) 24.75 Uiu/ml 5
Cystic Fibrosis by rheologic
5 stasis 1:22,225
on cardiac ultrasound. 100 Medications
Classical galactosemia were shifted
1 to IV diuretics
1:111,127 and inotropes; oral
20 digoxin was
Duarte galactosemia (D/G) 2 1:55,564 40
Other disorders
started. 2 IV antibiotics were given for possible
1:55,564 40
pulmonary
a
Based on an anticipated annual births of 2M and 100% coverage infection. The patient later on showed improvement, and was
eventually weaned off from ventilatory support, extubated,
Hemoglobin H-disease27,28 and anecdotal clinical experiences become more aware of newborn screening and take
have revealed catastrophic outcomes for homozygous Table 3. Cardiac
advantage of theEnzymes
program, these patients have a much better
variants of these diseases (personal communication with chance for earlyReference
detection
Rangeand treatment
(mmoL) leading to
Result
Maria Beatriz P Gepte and Ernesto Yuzon, August 2012). In significantly
Qualitative improved health outcomes. Expanded
PoSITIVE
California, 109 cases of hemoglobinopathies were detected screening
Troponin I for metabolic disorders will employ multiplex
representing 54.8% of the 199 Filipino newborns with a CK-MBby MS/MS, such that
testing 0-6.0 a single sample punch
1.14 for PKU
CK-ToTAl 21-232
confirmed diagnosis. It is anticipated that incorporation of will be simultaneously analyzed for more than 543
20 metabolic
hemoglobinopathies including Hemoglobin H Disease disorders including MSUD, Methyl Malonic Acidemia
through multiplex screening tests will significantly increase (MMA) and 20 others. In California, there were 6 cases of
hemoglobinopathy case detection in the Philippines, perhaps amino acid disorders (4 with PKU, 1 with variant
as high as 1860 cases annually, thereby significantly hyperphenylalaninemia and 4 with MSUD); 7 cases of
Figure 1. Electrocardiogram
improving health outcomesupon admission
through early diagnosis and organic acid disorders (5 with MMA, 1 with β-ketothiolase
treatment. deficiency (BKT) and 1 with Isobutyryl-CoA dehydrogenase
The Biochemical Genetics Unit of the Institute of deficiency (IBDHD); 10 cases of fatty acid oxidation
transferred to the intensive care unit (ICU) for ventilatory
Human Genetics29 contains a number of metabolic disorders (FAOD), 2 with Medium chain acyl-CoA
support and closer monitoring. on bedside cardiac ultrasound,
conditions in their listing of clinical cases including: PKU, dehydrogenase (MCAD) deficiency, 3 with Short chain acyl-
there was a finding of eccentric left ventricular hypertrophy,
MSUD, methylmalonic aciduria, citrullinemia, and many CoA dehydrogenase (SCAD) deficiency, 3 with Very Long
global hypokinesia with depressed overall systolic function
others. Unfortunately, these clinical patients usually present chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2
with concomitant spontaneous echo contrast on left ventricular
at a very late stage of disease often resulting in severe with other forms of fatty acid oxidation disorder); 1 case
(lV) cavity suggestive of rheologic stasis, the ejection fraction
complications
was 25%, with andmoderate
death. Patients
mitral with PKU and MSUD
regurgitation, are
moderate with partial biotinidase deficiency (BD), 1 case of classical
potentially more fortunate since screening tests for both
aortic regurgitation with aortic sclerosis, severe tricuspid of galactosemia and 2 cases of Duarte galactosemia. This
these disorders are currently included in the Philippine
regurgitation with mild pulmonary hypertension, pulmonary translates to an additional 580 disorders detectable each year
newborn screening
regurgitation, panel. pericardial
and minimal Thus, as effusion
parents orof pericardial
newborns in the Philippines
Figure including
2. Chest radiograph on140 cases of organic disorders,
admission

Vol. 46
VOL. 43 NO.
N0. 442009
2012 - VOL. 47 NO. 1 2013 ACTA MEDICA
ACTA MEDICA PHILIPPINA
PHIlIPPINA 27
13
Expanded Newborn Screening CASE REPORT

200 cases of fatty acid Heartoxidation Failure

disorders and and Short
240 otherStature ENBS has in been
a 43divided year-old into severalmale committees with specific
conditions. responsibilities:
Katerina
The data onT.cysticleyritanafibrosis1
, Ma. Czarlota M.There
is interesting. Acelajado-Valdenor
are no  1, Amado o. Tandoc III2 and
Advocacy/Promotions – toAgnes prepare D. Mejia
promotional
1

reported cases in the Philippines but there were 5 newborns programs prior to implementation.
diagnosed with 1Department
cystic fibrosis of Medicine,
in the College
CNSP.ofUpon Medicine and Philippine
review of General
 Hospital,
Regional University
Medical of the Philippines
Centers – to Manila
develop guidelines
the parental ethnicity of the Department of Pathology, College of Medicine, Universityforofthethe Philippines Manila centers that will be part of
2
5 newborns, it was discovered regional medical
that these patients were products of Filipino-Caucasian the follow-up system.
marriages. Given the increasing trend of mixed marriages,  Operations – to develop operational structure on
the addition of cystic fibrosis in the newborn screening panel fees, laboratory expansion and case follow-up.
may prove to be important for our population.
The benefit of the expanded screening program seems On August 29, 2012, the DOH Advisory Committee
clear but this can Presentation
be diminished of the casedue to the costs of require
approved regular laxative use.
the proposal There was also a All
for implementation. report
NSCs of two
are
This is a case of
implementation a 43-year-old
especially in a male Low- presenting with short
to Middle-Income more
being syncopal
reviewedepisodes. for capabilityHe wasfor brought
expansion.to another doctor
To date, in
stature and
(LMIC) heartsetting
country failure.likeThe the patient was admitted
Philippines. In theatpastthe in a private hospital
preparation where the assessment
for implementation, two workshops was stillfeaturing
a “heart
medicineseveral
decade, ward of the Philippine
cost-benefit analysis General Hospital (PGH)
and cost-effectiveness problem”.
international The experts
patient was haveagainbeen prescribedheld: unrecalled
1) an
for dyspnea.
studies This paper
were conducted to will
support investigate
expandedseveral issues:
screening. In medications
orientation/workshop and againforwas lost to disorders,
metabolic follow-up. whichThis time,was
differentiating
their study which congenital from acquired
evaluated the Californiahypothyroidism,
screening however,
attended symptoms
by geneticists were and persistent. He later consulted
neonatologists; and 2) an at
the relationship
program, Feuchtbaum between
and Cunningham hypothyroidism30 reported and
that the
the another local hospital, where
orientation/workshop he was admitted and
for hemoglobinopathies, managed
which was
cardiomyopathies,
benefits of using MS/MS and the therapeutic
outweighed theoptions
expenses in incurred
patients as a case of
attended byanemia
geneticistsand bronchial asthma. HeBoth
and hematologists. was workshops
discharged
with cardiomyopathy
after their analysis revealed secondary to hypothyroidism.
a benefit/cost ratio of US$ 9.32. slightly improved
were attended after four
by NSC heads, days,
NSC only to have recurrent
laboratory heart
and follow-up
In 70Theyears,
patientthehad costsbeen spentborn on fullMS/MStermnewborn
to a thenscreening
31-year- failure
nurses.symptoms, prompting
It is anticipated thatadmission
seventeenat multi-disciplinary
PGH.
old Gravida
would 4 Para 3 (G4P3),
be compensated for by the thenumber
4th of 9ofsiblings, withand
lives saved an Upon medical
regional admission the patient
centers will be was in mildas respiratory
organized follow-up
apparently unremarkable
morbidities avoided. Furthermore,
31 delivery atanother home facilitated
report stated by distress,
centers for withthestable
patientsvitaldiagnosed
signs and by no thenotenewborn
of fever. screening
Pertinent
a traditional
that it was more birthcost-efficient
attendant. He was noted
to screen a group to ofbe diseases
normal physical
program.exam Expandedfindingsnewborn
includedscreening
short stature, thick lips,tonon-
is expected be
at birth. rather
at once, The patient
than screen was allegedly
for single at par withseparately,
conditions age both pitting periorbital
implemented edema,
in phases indry2013.skin, a displaced apical impulse,
physically
and that mass andscreening
mentally with until MS/MS
eight years is evenoldcomparable
when he was to crackles on both lung fields, and bilateral non-pitting bipedal
said
othertoscreening
have stopped growingsuch
programs in height.
as that He for
wasbreast
broughtand to edema. There was also a 3 cm x 3 cm reducible umbilical
__________________
aprostate
privatecancer.
doctor, whose diagnosis was undisclosed, and he
32,33 hernia. However, there was no pallor, no neck vein distention,
was given medications to increase height, which the patient no apparent congenital malformations, no cardiac murmurs
Acknowledgments
took for only one monthConclusion with no improvement. Through the I wish
and no to acknowledge
clubbing. There and was thank
also no Dr. note Bradford Therrell, neck
of an anterior U.S.
years, the patient wasCNSPapparently well,that
although National
mass. Newborn Screening and Genetics Resource Center, for
Data from the showed there still
are of short
serious facilitating communications with the CNSP and for reviewing and
stature,
newbornwith thick lips,
disorders seencoarse
in Filipinofacial features
babies that andcannot
dry skin.be laboratory workup showed cardiomegaly with pulmonary
commenting on drafts of this manuscript. I also wish to thank Dr.
He was notably
detected by the slow current in ambulation.
newborn screening He was said tests toinhave
the congestion, thoracic dextroscoliosis, and atheromatous aorta by
Fred Lorey and Dr. Lisa Feuchtbaum, California Newborn Screening
bronchial
Philippines. asthma
Expandingat age the 15 years,
panel and since theninhe
of disorders thehad been
current chest
Program,radiograph,
for their and left ventricular
cooperation hypertrophy
and assistance by 12-lead
in sharing their
taking
Philippinesalbutamol
newborntablets screeningoccasionally
programfor to bouts of dyspnea
approximate that electrocardiogram
program data on Filipino (12-l newborns.
ECG) (Figures I wish 1 and 2), normocytic
to acknowledge the
occurring
in the CNSP onewill
to two
savetimes
lives annually.
and reduce unnecessary negative normochromic
support of the National anemiaCenter (Hgbfor 90Disease
mg/dl), dyslipidemia,
Prevention and
and Control
The outcomes
health patient’s in symptoms started in This
Filipino newborns. 2001 data
whenwas he used
was pre-renal azotemia
of the Department of (serum
Health and creatinine
the staff123 of themmol).
Newborn Electrolytes
Screening
reported to have sudden
for the development lossexpanded
of an of consciousness.
newbornDuring this
screening on admission showed slight hyponatremia, hypokalemia,
Reference Center, National Institutes of Health, University of the
time, the for
patient did not haveinany Philippines Manila.
and hypochloremia (serum Na 136, K 3.35, Cl 86). Blood gases
program implementation thesymptoms
Philippines. of heart failure;
no prior seizures, cyanotic episodes,
The data on Filipino newborns taken from the CNSP chest pain, headache, or revealed partially compensated metabolic alkalosis with mild
blurring of vision. He regained consciousness shortly after and _________ The patient was noted to be hypothyroid based
hypoxemia.
was presented to the National Technical Working Group for
was brought
Newborn to a private
Screening physician,atwhose
(NTWG-NBS) the DOH. assessment
This data washas a on elevated serum thyroid-stimulating hormone (TSH) and
References
“heart problem”. He was prescribed unrecalled medications markedly decreased serum free thyroxine (FT4). The exact
prompted a review and subsequently a formal 1. American Academy of Pediatrics, Newborn Screening Task Force.
taken for a few months and eventually discontinued when values are shown
Serving the family infrom
Tables
birth1toand 2.
the medical home: Newborn screening:
recommendation of expanded newborn screening program
the syncopal episode did not recur. Upon admission
a blueprint to the
for the future. wards,2000;
Pediatrics. the106(suppl):389-427.
patient was managed
to the DOH Advisory Committee on Newborn Screening last
In the next four years, the patient would develop as
2. having
Guthrie R, congestive
Susi A. A heart simple failure
phenylalaninefrommethodcardiomyopathy
for detecting
16 January 2012. A National Technical Working Group for phenylketonuria in large populations of newborn infants. Pediatrics.
intermittent, progressive exertional dyspnea and bipedal secondary to acquired hypothyroidism. oral loop diuretics,
Expanded Newborn Screening (NTWG-ENBS) was created 1963; 32:338-43.
edema. later on this would be accompanied by generalized angiotensin-converting
3. Padilla CD, Therrell BL. Screeningenzymenewborns (ACE) in theinhibitors, beta-
Asia-Pacific Region.
under the National Center for Disease Prevention and
body weakness, anorexia, and constipation, severe enough to blockers, statins,
In: Kumar andGenomics
D, ed. levothyroxine
and Health were started.
in the Electrolyte
Developing World.
Control (NCDPC) composed of personnel and staff from the Oxford: Oxford University Press, Inc.sections
2012:764-781.
correction was instituted. The of Endocrinology
Department of Health and representatives from different 4. Padilla CD, Basilio J, Oliveros Y. Newborn Screening: Research to
and Policy.
Cardiovascular
Acta Med
Diseases
Philipp. 2009;
were co-managing the patient
43(2):6-14.
concerned institutions.
Corresponding author: Ma. Czarlota The NTWG-ENBS
Acelajado-Valdenor, is tasked
M.D. to
Department together
5. PadillawithCD.the General
Towards Medicine
universal newbornservice.screening in developing
prepare theofnecessary
Medicine guidelines for the implementation of
Philippine General Hospital He soon developed
countries: obstacles and respiratory
the way forward. failure,
Ann Acadupon Medwhich the
Singapore.
expanded newborn screening in the country. The NTWG- 2008; 37(12Suppl):6-4.
Taft Avenue, Manila, 1000 Philippines considerations were acute pulmonary congestion, nosocomial
Telephone: +632 554-8488 6. Newborn Screening Reference Center (NSRC). Program Briefer.
pneumonia, to rule
[Online]. [cited 2012out
Dec].anAvailable
acute coronary event. He was later
from www.newbornscreening.ph.
Email: [email protected]

12 ACTA MEDICA
28 ACTA MEDICA PHILIPPINA
PHIlIPPINA Vol. 47
VOL. 46 NO. 4 2012 - VOL. 43 NO.
N0. 41 2009
2013
 Heart Failure and Expanded
Short StatureNewborn
in a 43 year-old male
Screening

Table
7. 1. Initial
Schulze laboratory
A, Lindner Results D,
M, Kohlmuller Olgemoller K, Mayatepek E, 21. Saadallah AA, Rashed MS. Newborn screening: experiences in the
Hoffman GF. Expanded newborn screening for inborn errors of Middle East and North Africa. J Inherit Metab Dis. 2007; 30(4):482-9.
metabolism CBC by electrospray ionization-tandem mass spectrometry:Blood chem. Urinalysisin newborn screening. J Inherit
22. Wilcken B. Recent advances ABG Metab Dis.
results, outcome and implications. Pediatrics. 2003; 111(6 Pt 1):1399-406. 2007; 30(2):129-33.
8. Benson JM,Reference Result and current status of newborn
Therrell BL Jr. History Reference 23. Result Color
Yamaguchi S. Newborn straw
Screening pH
in Japan: restructuring 7.408
for the new
Value
screening for hemoglobinopathies. Semin Perinatol. 2010; 34(2):134-44. Value era. Ann Acad Med Singapore. 2008; 37(12 Suppl ):13-5.
9. WBC 5-10
Lorey F, Cunningham 4.5
G, Vichinsky EP, etRBS 3.9-6.1
al. Universal newborn 24. 6.3Gu X, Wang Z, Transp
Ye J, Han L, Qiu ClearW. Newborn pCo2Screening 49.1in China:
4-6Hb H disease in California. GenetHGBA1C
RBCscreening for 4.27-6.07
Test. 2001; 5(2):93-100. 6.4phenylketonuria,
Sp Gravity 1.010
congenital hypothyroidism po2expanded screening.
and 70
10.HGBHoppe CC.120-150
Newborn screening 90 for hemoglobin BUN 2.6-6.4
disorders. Hemoglobin. 5.0Ann Acad Med Singapore.
pH 8.0 Suppl):107-4.
2008; 37(12 HCo3 31.3
HCT2011; 35(5-6):556-64.
0.38-0.48 0.27 CREA 53-115 25. 123Yoon HR, Lee KR, Sugar Kang S, et al.NEGScreening ofo2 sat
newborns and93.6
high-risk
11.MCVWilcken B, 80-100
Wiley V,FlHammond J, Carpenter K. AlB
Screening newborns 34-50
for 32group of childrenProtein NEG
for inborn metabolic Fio2using tandem
disorders 21% mass
MCH 27-31
inborn errors metabolism by tandem massTAG
of PG spectrometry. N 0.34-1.7
Engl J 0.82
spectrometry in RBC 0-1
South Korea: a three-year Temp
report. 36.9 2005;
Clin Chim Acta.
MCHC
Med. 2003; 320-360 G/l
348(23):2304-12. HDl 0.91-1.56 0.67
354(1-2):167-80. WBC 0-2
12.RDWBodamer OA, Hoffman GF, Lindner M. Expanded
11.5-15.5% lDlnewborn screening 1.1-3.8
in 26. 4.21
Han M, Jun SH, CastSong SH, Park KU, Kim JQ, Song J. UsePBS of tandem mass
PlTEurope 2007. J Inherit Metab Dis.Inc
200-400 2007; 30(4):439-44.
ToTAl CHol 4.2-5.2 spectrometry Epith
5.25 for newborn
cell screening Rareof 6 lysosomal storage disorders in
Slight poikilocytosis,
13.RETIC
Therrell BL,0.005-0.015
Adams J. Newborn screening in AST North America. J Inherit
15-37 95a Korean population.
BacteriaKorean J Lab Med. 2011; 31(4):250-6.
occ’l acanthocytes, ovalocytes,
SEGMetab Dis. 50-70%
2007; 30(4):447-65.
48 AlT 30-65 27. 91Vichinsky E. Mucus
Advancesth in the treatment
Rare of alpha-thalassemia. Blood
slight toxic granulation,
14. Huang HP, Chu KL, Chien YH, et al. Tandem mass neonatal screening Rev. 2012; 26 Suppl 1:S31-4.
lYMPH 20-44% 50 Alk po4 184 Crystals Rare
in Taiwan—Report from one center. J Formos Med Assoc. 2006; 28. Lal A, Goldrich ML, Haines DA, Azimi M,slight Singeranisocytosis
ST, Vichinsky EP.
MoNo 2-9% 2 NA 140-148 136.9 Am urates
105(11):882-6. Heterogeneity of hemoglobin H disease in childhood. N Engl J Med.
Eo 0-4% 0 K 3.6-5.2 3.35
15. Han LS, Ye J, Qiu WJ, Gao XL, Wang Y, Gu XF. Selective screening for 2011; 364(8):710-8.
BASo 0-2%
inborn errors of metabolism on
Cl using tandem100-108
0 clinical patients mass
86
29. Padilla CD, de la Paz EM. Genetic Services and testing in the
BlAST
spectrometry0%in China: a four 0year report. J CA++ Inherit Metab Dis.2.12-2.52
2007; 2.37
Philippines. J Community Genet. 2012. DOI 10.1007/s12687-012-0102-1.
30(4):507-14. P 30. 2.27
Feuchtbaum L, Cunningham G. Economic evaluation of tandem mass
16. Lindmer M, Hoffman GF, Matern D. Newborn MG++ 0.74-1
screening for disorders 0.83
spectrometry screening in California. Pediatrics. 2006; 117(5 Pt 2):S280-6.
of fatty acid oxidation: experience and recommendations from an expert 31. Venditti LN, Venditti CP, Berry GT, et al. Newborn screening by tandem
meeting. J Inherit Metab Dis. 2010; 33(5):521-6. mass spectrometry for medium-chain Acyl-CoA dehydrogenase
17. Feuchtbaum L, Carter J, Dowray S, Currier RJ, Lorey F. Birth prevalence deficiency: a cost-effectiveness analysis. Pediatrics. 2003; 112(5):1005-15.
of disorders detectable through newborn screening by race/ethnicity. fat
32. pad. Cardiac
Cipriano enzymes
LE, Rupar were
CA, Zaric GS. not consistent with
The cost-effectiveness of an acute
expanding
TableGenet
2. Thyroid
Med. 2012; Function Tests
14(11):937-45. newborn screening for up to 21 inherited metabolic disorders using
coronary event (Table 3), however, intravenous (IV) heparin
18. Watson MS. Current Reference of
status newborn screening:
Value decision-making
Result tandem mass spectrometry: results from a decision-analytic model.
about the conditions to include in screening programs. Ment Retard Dev (overlapping
Value Health.with
2007;oral warfarin) was still given to cover for
10(2):83-97.
Free T4 (0.8-2.0) 0.02 ng/dl
Disabil Res Rev. 2006; 12(4):230-5. the
33. presence of aJC,possible
Schoen EJ, Baker Colby CJ, lVTo TT. thrombus
Cost-benefitas demonstrated
analysis of universal
TSH (0.4-6.0) 24.75 Uiu/ml
19. Loeber JG. Neonatal screening in Europe: the situation in 2004. J Inherit by rheologic
tandem massstasis on cardiac
spectrometry for newborn ultrasound. Medications
screening. Pediatrics. 2002;
Metab Dis. 2007; 30(4):430-8. 110(4):781-6.
were shifted to IV diuretics and inotropes; oral digoxin was
20. Borrajo GJ. Newborn screening in Latin America at the beginning of the
21st century. J Inherit Metab Dis. 2007; 30(4):466-81. started. IV antibiotics were given for possible pulmonary
infection. The patient later on showed improvement, and was
eventually weaned off from ventilatory support, extubated,

Table 3. Cardiac Enzymes

Reference Range (mmoL) Result
Qualitative PoSITIVE
Troponin I
CK-MB 0-6.0 1.14
CK-ToTAl 21-232 543

Figure 1. Electrocardiogram upon admission

transferred to the intensive care unit (ICU) for ventilatory

support and closer monitoring. on bedside cardiac ultrasound,
there was a finding of eccentric left ventricular hypertrophy,
global hypokinesia with depressed overall systolic function
with concomitant spontaneous echo contrast on left ventricular
(lV) cavity suggestive of rheologic stasis, the ejection fraction
was 25%, with moderate mitral regurgitation, moderate
aortic regurgitation with aortic sclerosis, severe tricuspid
regurgitation with mild pulmonary hypertension, pulmonary
regurgitation, and minimal pericardial effusion or pericardial Figure 2. Chest radiograph on admission

Vol. 46
VOL. 43 NO.
N0. 442009
2012 - VOL. 47 NO. 1 2013 ACTA MEDICA
ACTA MEDICA PHILIPPINA
PHIlIPPINA 29
13
Expanded Newborn Screening CASE REPORT

Heart Failure and Short Stature in a 43 year-old male

Katerina T. leyritana1, Ma. Czarlota M. Acelajado-Valdenor1, Amado o. Tandoc III2 and Agnes D. Mejia1
1
Department of Medicine, College of Medicine and Philippine General Hospital, University of the Philippines Manila
2
Department of Pathology, College of Medicine, University of the Philippines Manila

Presentation of the case require regular laxative use. There was also a report of two
This is a case of a 43-year-old male presenting with short more syncopal episodes. He was brought to another doctor
stature and heart failure. The patient was admitted at the in a private hospital where the assessment was still a “heart
medicine ward of the Philippine General Hospital (PGH) problem”. The patient was again prescribed unrecalled
for dyspnea. This paper will investigate several issues: medications and again was lost to follow-up. This time,
differentiating congenital from acquired hypothyroidism, however, symptoms were persistent. He later consulted at
the relationship between hypothyroidism and the another local hospital, where he was admitted and managed
cardiomyopathies, and the therapeutic options in patients as a case of anemia and bronchial asthma. He was discharged
with cardiomyopathy secondary to hypothyroidism. slightly improved after four days, only to have recurrent heart
The patient had been born full term to a then 31-year- failure symptoms, prompting admission at PGH.
old Gravida 4 Para 3 (G4P3), the 4th of 9 siblings, with an Upon admission the patient was in mild respiratory
apparently unremarkable delivery at home facilitated by distress, with stable vital signs and no note of fever. Pertinent
a traditional birth attendant. He was noted to be normal physical exam findings included short stature, thick lips, non-
at birth. The patient was allegedly at par with age both pitting periorbital edema, dry skin, a displaced apical impulse,
physically and mentally until eight years old when he was crackles on both lung fields, and bilateral non-pitting bipedal
said to have stopped growing in height. He was brought to edema. There was also a 3 cm x 3 cm reducible umbilical
a private doctor, whose diagnosis was undisclosed, and he hernia. However, there was no pallor, no neck vein distention,
was given medications to increase height, which the patient no apparent congenital malformations, no cardiac murmurs
took for only one month with no improvement. Through the and no clubbing. There was also no note of an anterior neck
years, the patient was apparently well, although still of short mass.
stature, with thick lips, coarse facial features and dry skin. laboratory workup showed cardiomegaly with pulmonary
He was notably slow in ambulation. He was said to have congestion, thoracic dextroscoliosis, and atheromatous aorta by
bronchial asthma at age 15 years, and since then he had been chest radiograph, and left ventricular hypertrophy by 12-lead
taking salbutamol tablets occasionally for bouts of dyspnea electrocardiogram (12-l ECG) (Figures 1 and 2), normocytic
occurring one to two times annually. normochromic anemia (Hgb 90 mg/dl), dyslipidemia, and
The patient’s symptoms started in 2001 when he was pre-renal azotemia (serum creatinine 123 mmol). Electrolytes
reported to have sudden loss of consciousness. During this on admission showed slight hyponatremia, hypokalemia,
time, the patient did not have any symptoms of heart failure; and hypochloremia (serum Na 136, K 3.35, Cl 86). Blood gases
no prior seizures, cyanotic episodes, chest pain, headache, or revealed partially compensated metabolic alkalosis with mild
blurring of vision. He regained consciousness shortly after and hypoxemia. The patient was noted to be hypothyroid based
was brought to a private physician, whose assessment was a on elevated serum thyroid-stimulating hormone (TSH) and
“heart problem”. He was prescribed unrecalled medications markedly decreased serum free thyroxine (FT4). The exact
taken for a few months and eventually discontinued when values are shown in Tables 1 and 2.
the syncopal episode did not recur. Upon admission to the wards, the patient was managed
In the next four years, the patient would develop as having congestive heart failure from cardiomyopathy
intermittent, progressive exertional dyspnea and bipedal secondary to acquired hypothyroidism. oral loop diuretics,
edema. later on this would be accompanied by generalized angiotensin-converting enzyme (ACE) inhibitors, beta-
body weakness, anorexia, and constipation, severe enough to blockers, statins, and levothyroxine were started. Electrolyte
correction was instituted. The sections of Endocrinology
and Cardiovascular Diseases were co-managing the patient
Corresponding author: Ma. Czarlota Acelajado-Valdenor, M.D.
Department of Medicine together with the General Medicine service.
Philippine General Hospital He soon developed respiratory failure, upon which the
Taft Avenue, Manila, 1000 Philippines considerations were acute pulmonary congestion, nosocomial
Telephone: +632 554-8488 pneumonia, to rule out an acute coronary event. He was later
Email: [email protected]

12 ACTA MEDICA
30 ACTA MEDICA PHILIPPINA
PHIlIPPINA Vol. 47
VOL. 46 NO. 4 2012 - VOL. 43 NO.
N0. 41 2009
2013