Measures of cognitive, frontal lobe (executive), behavioral and motor function were administered to 18 children (aged 12-101 months) with phenylketonuria followed at the University of Rochester School of Medicine, NY. Current phenylalanine levels were within recommended range (120-485 mcmol/1) in 65%, and lifetime levels ranged from 206-1331 (mean, 499). “Individual variation” (SD of lifetime level) ranged from 76-547 (av, 270). Lower current phenylalanine (PHA) levels were associated with higher cognitive functioning in children older than 3 yrs. Higher current and average levels correlated with more difficult temperament on behavior scales. Motor function was impaired in PKU children with current PHA levels above 360 mcmol/1, and lower motor scores tended to correlate with older age and current PHA levels. Decreased executive functioning was strongly correlated with increased individual variation in lifetime average PHA levels. Maintained PHA levels of <360 mcmol/1 may be necessary for optimal outcome in PKU children. 
COMMENT. These data support a strict dietary control of PKU, maintaining phenylalanine levels below 360 mcmol/1 throughout childhood. Executive behavior and motor development, both dependent on frontal lobe function, are correlated with the degree of individual variation in phenylalanine levels during childhood. An increased incidence in attention deficit hyperactivity disorder might be expected in PKU children with frontal lobe dysfunction.