Quantitative studies on the urinary excretion of unconjugated aromatic acids in phenylketonuria

The urinary excretion of unconjugated aromatic acids (phenylglycollic (mandelic), 2-hydroxyphenylacetic, phenyllactic, phenylpyruvic, 4-hydroxy-phenyllactic and 4-hydroxyphenylpyruvic) by 41 cases of phenylketonuria, by 2 phenylketonuric children with apparently normal intelligence and by a phenylketonuric woman who was identified by the routine screening of antenatal patients for phenylketonuria has been studied. None of these patients was receiving a low phenylalanine diet when the urine collections were made. Possible correlations between the degree of organic aciduria and the patient's degree of disability have been examined. The excretion of tyrosine metabolites (4-hydroxyphenyllactic and 4-hydroxyphenylpyruvic acids, without homogentisic aciduria) was a striking feature in all except one of the patients studied. These metabolites appear to be derived partly from dietary phenylalanine, and partly from endogenous tyrosine. The presence of some residual phenylalanine 4-hydroxylase (EC 1.14.3.1) activity is suggested, even in the most retarded patients. The possible location of this residual enzyme activity cannot be specified. 4-Hydroxyphenylpyruvate oxidase (EC 1.14.2.2) also appears to be inhibited in phenylketonuria. The study of a wide range of biochemical parameters may improve our ability to differentiate the atypical forms of phenylketonuria.