Recent data suggest that children with phenylketonuria (PKU) and poor metabolic control may have an increased prevalence of attentional dysfunction. However, few formal studies have addressed this topic in detail. We reviewed the medical records of 38 school-aged children with early and continuously treated PKU to determine the prevalence of stimulant use for attentional dysfunction, and to determine the relationship between metabolic control and attentional symptoms. Twenty-six per cent of the PKU children used a stimulant medication for attentional dysfunction. This is significantly higher than in an age- and sex-matched control group consisting of children with type I diabetes mellitus (6.5%, p <0.006), and also considerably higher than population norms for attention deficit hyperactivity disorder (ADHD) (5%). We also found a significant relationship between phenylalanine levels and stimulant use or attentional symptoms. Mean plasma phenylalanine concentration was 486 micromol/L in the non-stimulant-using group and 792 micromol/L in the stimulant-using group (p <0.02). Mean phenylalanine concentration was 462 micromol/L in the group not reporting attentional symptoms, and was 702 micromol/L in the symptomatic group (p <0.05). Parents of the stimulant-using children felt that the stimulants were efficacious in treating their child's attentional symptoms. Stimulant use and parent reports of attentional dysfunction are quite common in our PKU patients and appear to be strongly related to higher phenylalanine concentrations.

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.

LS, Davidson PW. Factors affecting cognitive, motor, executive and behavioral functioning in children with phenylketonuria. Acta Paediatr 1998; 87: 565-70. Stockholm. ISSN 0803-5253We 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 Ն3 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 Ͼ360 mmol/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 Ͻ 360 mml/l may be necessary for optimal performance in children with phenylketonuria. ٖBehavior, motor function, neuropsychology, outcome, phenylketonuria