THE RELATIONSHIP OF GENOTYPE TO PHENOTYPE IN PHENYLALANINE-HYDROXYLASE DEFICIENCY

Seventy-two adults with phenylketonuria were evaluated to investigate the genotypic relationship to phenotype. Patient data were collected b y chart review and medical follow-up as well as current psychological evaluation. Nineteen diagnosed neonatally had remained on a phenylalan ine-restricted diet all their lives, whereas 34 who were also diagnose d on newborn screening had discontinued dietary restriction during chi ldhood, Nineteen others who were born prior to newborn screening were diagnosed later than the newborn period on clinical grounds but have r emained on dietary restriction. Comparison between intellectual abilit y, academic achievement, and mental illness was made with degree of di et control as defined by range of blood phenylalanine levels over time . Diet discontinuation in childhood did not significantly lower IQ per se but appeared to diminish academic achievement, The lowest IQ score s mere associated with poor dietary restriction of phenylalanine in th e diet during childhood. While there appears to be a strong genotypic relationship to phenotypic metabolic parameters in phenylketonuria, th ere does not seem to be a similar relationship to intellectual ability in adults, Mutation R408W was not strongly related to the occurrence of mental illness in this sample. We conclude that dietary restriction of phenylalanine neonatally and good control contributed to normal in tellectual development. Continuation of dietary treatment into adultho od appeared to improve academic achievement in patients with severe ph enylalanine hydroxylase mutations. (C) 1997 Academic Press.