STUDIES ON PHENYLKETONURIA. I. RESTRICTED PHENYLALANINE INTAKE IN PHENYLKETONURIA 1

Abstract

The relationship between the biochemical defect in the.hereditary condition, phenylketonuria (phenylpyruvic oligophrenia), and the accompanying mental defect is at the present time obscure. The work of F6lling (1) and Jervis (2, 3) has shown that the inheritance of the condition appears to be controlled by a single autosomal recessive gene. A series of investigations by Jervis and his collaborators (4-1 ) has demonstrated that the biochemical defect lies in a failure of the affected individuals to oxidize phenylalanine to tyrosine in the normal fashion. The major abnormal metabolites known to occur in this condition can arise as a logical consequence of the accumulation of large amounts of phenylalanine and the channelling of this phenylalanine into abnormal pathways. These metabolites are phenylalanine itself (8), phenylpyruvic acid (8), phenyllactic acid (8), and phenylacetylglutamine (12). Abnormally high levels of phenylalanine are found in serum (20 to 60 mg. per 100 ml.) and cerebrospinal fluid (6 to 8 mg. per 100 ml.) (9) and phenylpyruvic acid has been demonstrated in the serum of affected individuals (10). Recently it has been found that lesser amounts of other abnormal metabolites are excreted. These include o-hydroxyphenylacetic acid (13, 14) and products derived from tyrosine (13, 15) and tryptophan (15, 16). The manner in which these substances arise will be considered in later communications.