Tetrahydrobiopterin (BH 4 ) in PKU: effect on dietary treatment, metabolic control, and quality of life

Background Tetrahydrobiopterin (BH 4 )‐sensitive phenylketonuria (PKU) can be treated with sapropterin dihydrochloride. We studied metabolic control and health‐related quality of life (HRQoL) in PKU patients treated with BH 4 . Subjects and methods Based on the review of neonatal BH 4 test results and mutation analysis in 41 PKU patients, 19 were identified as potentially BH 4 ‐sensitive (9 females, 10 males, age 4–18 years). We analyzed phenylalanine (phe) concentrations in dried blood samples, nutrition protocols, and HRQoL questionnaires (KINDL ® ) beginning from 1 year before, during the first 42 days, and after 3 months of BH 4 therapy. Results Eight BH 4 ‐sensitive patients increased their phe tolerance (629 ± 476 vs. 2131 ± 1084 mg, p  = 0.006) while maintaining good metabolic control (phe concentration in dried blood 283 ± 145 vs. 304 ± 136 μM, p  = 1.0). Six of them were able to stop dietary protein restriction entirely. BH 4 ‐sensitive patients had average HRQoL scores that were comparable to age‐matched healthy children. There was no improvement in HRQoL scores after replacing classic dietary treatment with BH 4 supply, although personal reports given by the patients and their parents suggest that available questionnaires are inappropriate to detect aspects relevant to inborn metabolic disorders. Discussion BH 4 can allow PKU patients to increase their phe consumption significantly or even stop dietary protein restrictions. Unexpectedly, this does not improve HRQoL as assessed with KINDL ® , partly due to high scores even before BH 4 therapy. Specific questionnaires should be developed for inborn metabolic disorders.