Studies in man using semi-tracer doses of deuterated phenylalanine and tyrosine: implications for the investigation of phenylketonuria using the deuterated phenylalanine load test

Abstract

In classical phenylketonuria there is a virtual absence of phenylalanine hydroxylase activity in the liver, the organ usually responsible for catabolism of excessive dietary phenylalanine. The accumulation of phenylalanine, and possibly some of its metabolites, results in severe mental retardation. Consequently, great effort is put into detecting the disorder in the first few weeks of life so that it can be treated by restriction of phenylalanine intake. Unfortunately, it is sometimes difficult to classify cases detected by screening in the newborn period and there appears to be an almost continuous gradation from the classical phenylketonuric to the normal individual. Attempts to differentiate sub-groups of the disease by estimating phenylalanine hydroxylase in liver biopsy specimens have been made at various centres but the situation still remains confused. The normal phenylalanine loading tests using oral doses of 100–200 mg/kg body weight are difficult to interpret and, although the results of intravenous loading tests are more amenable to rigorous mathematical treatment (Woolf, Cranston and Goodwin, 1967), this has not proved to be an acceptable procedure for routine use with the newborn child.