AMINOACIDOPATHIES

METABOLIC DEFECT CONSEQUENCE MANIFESTATION TREATMENT

Phenylketonuria Inherited as an ART Absence of enzyme PAH — PHE levels: > 1200 mmol/L — Brain problems — Fetal effects of maternal PKU
— Upper limit for PHE level in — Musty odor of urine is prevented if the mother is
newborns: 120 mmol/L (2 mg/dL) — Retarded mental development maintained on PHE-restricted
— Untreated PKU: > 2.4 mM/L and microcephaly in infants diet
Enzyme Deficiency Deficiency in the enzymes — Elevated levels of PHE — Goal of the treatment:
needed for the regeneration — Deficient production of maintain PHE blood levels
and synthesis of neurotransmitters from TYR and between 2-10 mg/dL (120-600
tetrahydrobiopterin (BH4) TRP mol/L)
— Avoid foods that are rich in
protein
Tyrosinemia Type I Low levels of enzyme — Tyrosine and tyrosine catabolites — Failure to thrive — Low-protein diet
fumarylacetoacetate in urine — Diarrhea
hydrolase — Vomiting
— Jaundice
— Cabbage-like odor
— Distended abdomen
— Swelling of legs
— Increased predisposition for
bleeding
Type II Deficiency of enzyme tyrosine — Mental retardation (50%)
aminotransferase — Excessive tearing
— Photophobia
— Eye pain and redness
— Painful skin lesions on the palms
and soles of the feet
Type III Deficiency of the enzyme 4- — Mental retardation
hydroxyphenylpyruvate — Seizures
dioxygenase — Periodic loss of balance and
coordination
Alkaptonuria Inherited as an Lack of the enzyme — Defect in the metabolism of — Urine turns brownish-black — High-dose Vit C
ARG, (HGD gene) homogentisate oxidase tyrosine and phenylalanine when mixed with air (due to
HGA)
— Ochronosis (pigments in tissues)
— Arthritis-like degeneration
— Dark spots on the sclera
— Pigments in the cartilage of the
ears, nose, and tendons, and
extremities
Maple Syrup Absence or reduced activity — Defect in the metabolism of LEU, — Maple syrup or burnt sugar — Protein-restrictive diet to
Urine Disease of enzyme branched-chain- ILE, and VAL resulting in odor of the urine, breath, and lower the levels of
(MSUD) ketoacid decarboxylase accumulation in blood, urine, and skin accumulating isovaleric acid,
CSF — Infants: lethargy, vomiting, lack which is toxic to the CNS
of appetite, and failure to thrive
— CNS symptoms: muscle rigidity,
stupor, and respiratory
irregularities
 — Severe mental retardation,
seizures, acidosis, and
hypoglycemia
— Death is left untreated
Isovaleric Anemia Deficiency of the enzyme — Defect in the metabolism of the — Sweaty feet odor — Protein-restrictive diet to
isovaleryl-CoA branched-chain amino acid LEU — In severe cases, it could cause lower the levels of
dehydrogenase damage to the brain and accumulating isovaleric acid,
nervous system which is toxic to the CNS
— In infants: failure to thrive,
vomiting, lethargy that can
progress to seizures, coma, and
death
Homocystinuria Lack of the enzyme — Elevated plasma and urine levels — Infants: relatively healthy — Dietary restriction of
cystathionine- synthetase of MET and of the precursor — Late childhood: osteoporosis, methionine (low protein) as
homocysteine dislocated lenses in the eye, and well as high doses of vitamin
mental retardation B6
— Multisystemic disorders of the
CT, muscles, CNS, thinning and
weakening of bones, and
thrombosis if left untreated
Citrullinemia Type I- GD Urea cycle disorder — — — High-calorie, protein-
Type II- GD — — restrictive diet
— Arginine supplementation
— Administration of sodium
benzoate and sodium
phenylacetate
Argininosuccinic Genetic Disease Lack of the enzyme — Elevated levels of argininosuccinic — In newborn: lethargy and — High-calorie, protein-
Aciduria argininosuccinic acid lyase also cause buildup of the amino unwillingness to eat restrictive diet
acid citrulline in the blood — Arginine supplementation
— Urea cycle cannot proceed — Administration of sodium
normally and nitrogen benzoate and sodium
accumulates in the blood in the phenylacetate
form of ammonia. Ammonia is
neurotoxic & hepatotoxic.
Cystinuria Defect in the amino acid — Inadequate reabsorption of — Hematuria, pain in the side due — Increasing the volume of urine
transport system rather than cystine during the filtering to kidney pain, and UTI to reduce the concentration
a metabolic enzyme process in the kidneys, resulting of cystine in the urine and
deficiency in an excessive concentration of reduce its precipitating from
this amino acid the urine and forming stone
— Cystine precipitates out of the
urine and forms stones in the
kidneys, ureters, or bladder