NEUROPSYCHOLOGICAL OUTCOME OF EXPERIMENTAL MANIPULATION OF PHENYLALANINE INTAKE IN TREATED PHENYLKETONURIA

Blood phenylalanine concentrations were experimentally increased for 3 months by means of a phenylalanine-complemented amino acid supplement , in a group of 16 children aged 10-16 years with classical phenylketo nuria who had been treated early and who had remained on the restricte d diet. Average concentrations achieved during challenge were between 1000 and 1300 mu mol/L. Psychological outcome was measured by a neurop sychological battery consisting of tests of verbal and spatial memory, attention and fine motor coordination. A triple-blind, repeated measu res, randomized, crossover design was adopted to control for practice and expectancy effects. Subjects were assessed at baseline and at the end of the first and second phenylalanine manipulation periods. Signif icant interactions (ANOVA) emerged as predicted Eor:phenylalanine conc entrations, but similar crossover effects were not found for any of th e neuropsychological tests. The results suggested that medium-term hyp erphenylalaninaemia in treated PKU is not harmful to psychological fun ctioning in older children and adolescents who have been continuously treated up to and beyond age 10 years, though the susceptibility of ex ecutive functions needs to be further researched. The findings add som e weight to the idea that by late childhood the vulnerability of the n ervous system to the neurotoxic influence of phenylalanine may be much reduced.