Factors affecting cognitive, motor, behavioral and executive functioning in children with phenylketonuria.

We administered measures of cognitive, frontal lobe (executive), behavioral and motor functioning to 18 children with classical phenylketonuria, aged 12-101 months, in order to determine the relationship of age, current and lifetime average phenylalanine levels, and individual variation (standard deviation of lifetime average levels) to these functions. On measures of cognitive function, in children > or = 3 y of age lower current phenylalanine levels were associated with higher cognitive functioning. On a behavioral temperament scale designed for normal children, we found that higher current and average phenylalanine levels correlated with more difficult temperament. Motor function was also poorer in children with phenylketonuria, and was most impaired in children with current phenylalanine levels >360 micromol/l. We also identified a previously unreported correlation between increased individual variation and poorer executive function performance, a finding that may raise new management concerns about level fluctuations. Maintenance of phenylalanine levels <360 micromol/l may be necessary for optimal performance in children with phenylketonuria.