Neuropsychological outcome of experimental manipulation of phenylalanine intake in treated phenylketonuria.

[classical 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 phenylketonuria who had been treated early and who had remained on the restricted diet . Average concentrations achieved during challenge were between 1000 and 1300 mumol /L . Psychological outcome was measured by a neuropsychological battery consisting of tests of verbal and spatial memory , attention and fine motor coordination . A triple-blind , repeated measures , 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 . Significant interactions (ANOVA ) emerged as predicted for phenylalanine concentrations , but similar crossover effects were not found for any of the neuropsychological tests . The results suggested that medium-term hyperphenylalaninaemia in treated PKU is not harmful to psychological functioning in older children and adolescents who have been continuously treated up to and beyond age 10 years , though the susceptibility of executive functions needs to be further researched . The findings add some weight to the idea that by late childhood the vulnerability of the nervous system to the neurotoxic influence of phenylalanine may be much reduced .