Question

Discuss an aminoacidopathy, including the biochemical abnormality, and physiological response. Some suggestions are Phenylketonuria, Tyrosinemia, Alkaaptonuira, Maple Syrup Urine Disease, Homocystinuria, Cystinuria

Answer 1

Phenylketonuria

Phenylalanine is an essential aromatic amino acid.Phenylalanine metabolism involves conversion of phenylalanine to tyrosine by the enzyme phenylalanine hydroxylase.This reaction also requires tetrahydrobipterin which is converted to dihydrobiopterin.Again tetrahydrobiopterin is regenerated from dihydrobiopterin using a reductase enzyme.

Phenylketonuria type 1 occurs due to deficiency of the enzyme phenylalanine hydroxylase -either the enzyme is not synthesised or a defective enzyme is synthesised.It is an autosomal recessive disease.Incidence is 1 in 10000 births.

Type 2 and 3 is do to deficiency of enzyme dihydrobiopterin reductase.Type 4 and 5 is due to deficiency of enzyme synthesising biopterin.

Since phenylalanine is not converted to tyrosine, phenylalanine accumulates in blood.Also alternate pathways are opened by which phenyl lactate, phenyl pyruvate and phenyl acetate are produced.These are excreted in urine.

Clinical manifestations- Child will be mentally retarded.There will be hypo pigmentation( due to inhibition of tyrosinase), mousy body odour(due to presence of phenyl lactic acid in sweat),agitation, tremor,convulsions (phenylalanine interferes with neurotransmitter synthesis).There can be muscle hypotonia and microcephaly with developmental retardation.

Lab diagnosis - blood levels of phenylalanine will be more than 20mg/DL(normal is 1 mg/dl)),ferric chloride test(addition of ferric chloride in urine give blue green colour with phenylketones,Guthrie test.

Treatment -Early initiation of treatment is needed because diminishing of IQ can occur with delay in treatment Treatment is to provide diet low in phenylalanine(10 -20mg/kg/day).This is to be followed in first decade of life after which normal diet can be given.Also when the female patient gets pregnant ,this diet is to be followed.