Correlation of Age-Specific Phenylalanine Levels on Intellectual Outcome in Patients with Phenylketonuria

This study includes data collected from a retrospective chart review of patients with phenylketonuria treated at the University of Utah Metabolic Clinic. Among theapproximately 175 patients treated for phenylketonuria at this clinic, 55 patients (28 female) met the inclusion criteria for the present study. Based on the diagnostic Phelevel, 66.7% were classified as having classic phenylketonuria, 18.5% with moderate phenylketonuria, and 14.8% with mild phenylketonuria. Subjects’ cognitive status was measured with one of three neuropsychological tests: Wechsler Intelligence Scale for Children third and fourth editions and the Wechsler Adult Intelligence Scale third edition. Due to structural differences among the tests, only the Verbal Comprehension Index, Block Design subtest, and Symbol Search subtest were compiled and included for statistical analysis. Quality of metabolic control was assessed with blood and plasma phenylalanine levels throughout each patient’s life. Three developmental age periods were defined (0-5 years, 6-10 years, and \u3e10 years). The index of dietary control (IDC), defined as mean of median phenylalanine levels for each patient in 12-month intervals, was calculated for each developmental period. The mean standard deviation (SD) of blood phenylalanine levels and mean number of blood phenylalanine samples were also assessed in 12-month intervals. Linear regression analysis was used to evaluate the most recent measures of intelligence in relationship to IDC and mean SD blood phenylalanine levels duringdevelopmental periods. Logistic regression was also used to examine the association between mean number of phenylalanine samples during each developmental period and the likelihood of maintaining blood phenylalanine less than 360 μmol/L and within one SD of the IDC. Using multivariate linear regression, a model including IDC and number of samples from lifetime, 0-5 years, and 6-10 years were significantly associated withperceptual reasoning, but IDC regression coefficients were not significantly correlated. Multivariate logistic regression revealed a 32 percent decrease in risk of IDC exceeding the upper limit of the treatment range for each additional phenylalanine assessment per year between the ages of 6-10 years (p = 0.001). No association was observed between SD blood phenylalanine and cognitive outcomes or frequency of sampling during anydevelopmental periods