HYPERPHENYLALANINEMIA DUE TO PHENYLALANINE HYDROXYLASE COFACTOR DEFICIENCY

Abstract

A child with phenylketonuria diagnosed early developed severe hypotonia with minimal signs of spasticlty and retardation in all developmental patterns despite adequate dietary management. At 4 years of age, a liver biopsy was performed and the components of the phenylalanine hydroxylase system were measured in vitro. Normal levels of phenylalanine hydroxylase, dihydropteridine reductase and dihydrofolate reductase were found. However, there was only 5% of the normal level of active phenylalanine hydroxylase cofactor. This cofactor deficiency was also demonstrable in plasma and urine. Since the phenylalanine hydroxylase cofactor (tetrahydrobiopterin) is probably also necessary for the hydroxylation of tyrosine and tryptophan, the rate limiting steps in the biosynthesis of dopamine and norepinephrine and serotonin, this child may be suffering from a lack of these neurotransmitters.The child's phenylalanine hydroxylase activity has also been measured with a new in vivo method. In this procedure, hydroxylase activity is assayed by following the rate of formation of tritiated water from ring tritium labelled phenylalanine. Phenylalanine hydroxylase activity 1-5% of normal was detected in vivo confirming the incomplete block in the conversion of phenylalanine to tyrosine predicted by the in vitro assays on the liver biopsy.