Prefrontal dysfunction in early and continuously treated phenylketonuria

In this study, we tested the hypothesis that patients with early and contin uously treated phenylketonuria (PKU) are selectively impaired in cognitive functions dependent on the prefrontal cortex (PFC) over a wide age range. T hirty-six patients with PKU between 8 and 20 years of age and 36 controls m atched for age, sex, and educational level of both parents performed comput erized versions of tests shown to be sensitive to PFC functions. To assess specificity, we selected within each test measures shown to be specifically impaired by PFC damage as well as measures not specifically impaired by da mage to the PFC (control measures). A contrast sensitivity test was adminis tered to obtain additional and independent evidence for the mechanism propo sed to underlie the specific PFC deficits. Patients with early and continuo usly treated PKU demonstrated impairments on 3 of the 4 PFC measures but no t on any of the control measures. Furthermore, they were found to be signif icantly less sensitive to contrast than were the matched controls. Together , these results seem to confirm that specific deficits in PFC functions per sist in older patients with early and continuously treated PKU. The results with respect to the biochemical mechanism underlying these deficits were l ess clear. They do suggest, however, that some of the deficits may be ameli orated by stricter dietary treatment.