Aminoacidopathies

Name Phenylketonuria (PKU) Tyrosinemia Alkaptonuria Maple Syrup Urine Isovaleric Homocystinuria Argininosuccinic Cystinuria
Disease (MSUD) Acidemia Aciduria &
Citrullinemia
Trait autosomal recessive Familial metabolic One of the original hereditary Inherited Genetic defect in the
trait disorder “inborn errors of renal absorption
metabolism” mechanism
Type deficiency deficiency Biochemical defect absence or greatly deficiency Impaired activity Deficiency in urea Defect in amino acid
decrease cycle transport system
Enzyme phenylalanine fumaryl-acetoacetate homogentisate oxidase enzyme branched- Isovaleryl-CoA Cystathione beta- Arginosuccinic acid 20-30 fold ↑ in urinary
hydroxylase (PAH)/ hydrolase (tyrosinemia I); in the tyrosine catabolic chain alpha ketoacid building up synthase leading (ASA) lyase (leading excretion of cysteine;
phenylalanine-4-mono- tyrosine aminotransferase pathway decarboxylase, Isovaleric acid to to ↑ precursors to citrullinemia) ↑ excretion of lysine,
(tyrosinemia II);
oxygenase blocking leucine, toxic level, hemocystein and arginine and ornithine
4-hydroxyphenylpyruvic
(turns phenylalanine to isoleucine and damaging the methionine in due to def. resorption
acid oxidase
tyrosine) (tyrosinemia III) valine in UBC brain and nervous plasma & urine
system
Clinical retarded mental liver damage (infant); ochronosis (tissue failure to thrive “sweaty feet thrombosis, vomiting and high Formation of calculi or
findings development cirrhosis & carcinoma pigmentation) (death in 1st year), odor” osteoporosis, lens ammonia levels, stone (insoluble
muscular rigidity, (↑ glycine dislocation and sometimes mental cysteine precipitate in
mental retardation, conjugate of mental retardation (MR) kidney tubules)
keto-acidosis and isovaleric acid, retardation (MR)
hypoglycemia isovaleryl glycine)
Diagnosis >1200 umol/L of excretion of urine darkening of urine upon Maple syrup/ burnt Physical defects
Indicator phenylalanine in the tyrosine and its standing at room temp sugar odor of the develop gradually
blood; catabolities -in connective tissues urine, breath and with age
musty odor of urine seen microscopically skin.
-4mg/dl of leucine
Screening Guthrie Bacterial Modified Guthrie Citrulline is a
test Inhibition Assay (B. Test (4-azaleucine- diagnostic marker;
subtilis spores & β2- antagonist) dramatically ↑ in
thienylalanine -increase leucine citrullinemia,
antagonist) level overcome the milder ↑
[B.subtilis cannot grow activity of 4- Arginosuccinic
in agar plate containing azaleucine allowing aciduria (ASAuria)
β2-thienylalanine, but bacterial growth.
blood phenylalanine
level is higher the
4mg/dl counteracts the
antagonist β2-
thienylalanine and the
bacteria will grow (+).
Diagnosis HPLC HPLC (Amino acid Chromatography Cyanide-nitroprusside,
Test analysis) react sulfhydryl group