Sapropterin therapy increases stability of blood phenylalanine levels in patients with BH4-responsive phenylketonuria (PKU)

It has recently been demonstrated that variability in blood phenylalanine levels is inversely correlated with IQ and is a better predictor of IQ in early and continuously treated patients with phenylketonuria (PKU) than mean blood phenylalanine levels. This suggests that stability of blood phenylalanine should be a therapeutic goal in patients with PKU. The purpose of this study was to determine if treatment with sapropterin in patients with BH4-responsive PKU would increase the stability of blood phenylalanine levels. The records of all patients treated with sapropterin in the PKU Clinic at Children's Memorial Hospital in Chicago were examined retrospectively. Patients were included in the study if they were responsive to sapropterin during a 2- to 4-week challenge (reduction of blood phenylalanine level of at least 25% after 2 weeks of therapy or, in the case of patients with well-controlled blood phenylalanine at the time of testing, increased dietary phenylalanine tolerance by 4 weeks of treatment). A total of 37 subjects were eligible for inclusion (16 male; 21 female); the mean age was 12.6 years (range, 1.5-32.0). The total number of observations (phenylalanine levels) for all subjects was 1391 with a mean of 39 per subject (range, 13-96). Linear mixed modeling was utilized to estimate variances of the blood phenylalanine before (pre) and after (post) starting sapropterin. Likelihood ratio test was performed using SAS 9.1. Means and standard deviations for phenylalanine as estimated by the model were 6.67 mg/dl (4.20) and post 5.16 (3.78). The mean level post-sapropterin was significantly lower (p = .0002). The within-subject variances (mean and SD) of phenylalanine were: pre 6.897 (2.62) and post 4.799 (2.19). These two variances are significantly different with a p = .0017. We conclude that sapropterin therapy results in increased stability of blood phenylalanine levels. This effect is likely to improve cognitive outcome in BH4-responsive patients with PKU.