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