The challenge of long-term tetrahydrobiopterin (BH4) therapy in phenylketonuria: Effects on metabolic control, nutritional habits and nutrient supply

BH4-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 BH4-therapy. Retrospective analysis of mean dried blood Phe concentrations and their variability, food and nutrient intake in BH4-sensitive patients (n=8, 3f, age 6.0–16.6y) under classical dietary treatment for one year and during the three years after initiation of BH4. Phe concentrations of BH4-sensitve PKU patients remained within therapeutic range throughout the observation period, independent of therapeutic regime. Under BH4, Phe tolerance increased significantly (493.2±161.8mg/d under classical diet vs 2021.93±897.4mg/d two years under BH4; 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 BH4 a drop in micronutrient intake (vitamin D, folic acid, iron, calcium, iodine) could be revealed (P=0.005, P