The challenge of long-term tetrahydrobiopterin (BH(4)) therapy in phenylketonuria: Effects on metabolic control, nutritional habits and nutrient supply

BACKGROUND AND AIMS: BH(4)-sensitive phenylketonuria (PKU) patients relax their phenylalanine (Phe) restricted diet due to increased Phe tolerance, while keeping dried blood Phe concentrations with in the therapeutic range. We aimed to investigate metabolic control, eating habits and nutrient supply under long-term BH(4)-therapy. PATIENTS AND METHODS: Retrospective analysis of mean dried blood Phe concentrations and their variability, food and nutrient intake in BH(4)-sensitive patients (n = 8, 3f, age 6.0–16.6 y) under classical dietary treatment for one year and during the three years after initiation of BH(4). RESULTS: Phe concentrations of BH(4)-sensitve PKU patients remained within therapeutic range throughout the observation period, independent of therapeutic regime. Under BH(4), Phe tolerance increased significantly (493.2 ± 161.8 mg/d under classical diet vs 2021.93 ± 897.4 mg/d two years under BH(4); P = 0.004). Variability of Phe concentrations remained unchanged (mean SD; P = 1.000). Patients adjust their food choice and significantly increased their intake of cereals, potatoes, dairy products and meat (P = 0.019, P = 0.016, P = 0.016 and P = 0.016, respectively). Under diet changes after implementation of BH(4) a drop in micronutrient intake (vitamin D, folic acid, iron, calcium, iodine) could be revealed (P = 0.005, P < 0.001, P = 0.004, P = 0.001, P = 0.003, respectively). CONCLUSIONS: BH(4)-sensitive PKU patients can achieve good metabolic control under an adjuvant BH(4)- or a BH(4) monotherapy. The liberalized diet under BH(4) seems to jeopardize the quality of patients' nutrition, and these patients require close follow-up and special nutrition education to minimize the risk for imbalanced diet and nutrient deficiencies.