Phenylketonuria (PKU) is caused by mutation of the phenylalanine hydroxylase gene → Phenylalanine hydroxylase deficiency → Failure of conversion of phenylalanine to tyrosine in the liver →High serum concentration of phenylalanine which is neurotoxic →Progressive cerebralmyelination. In addition the minor pathways of phenylalanine metabolism produce phenyl pyruvic acid (“phenylketone”) and phenyl acetic acid which are excreted via the urine.
Phenylketonuria (PKU) is clinically characterized by:
Progressive mental deterioration usually pronounced by age 1.
Hyperactivity and other neurologic abnormalities.
Decreased pigmentation of hair, eyes and skin. (Children are characteristically blond and blue-eyed).
Mousy body odour from phenylacetic acid in urine and sweat.
Phenylketonuria (PKU) can be successfully treated by a phenylalanine–free diet. Screening tests for serum phenylalanine or urinary catabolites are ordinarily performed on the 3rd or 4th day of life.