Long-term follow-up of patients with phenylketonuria receiving tetrahydrobiopterin treatment

Treatment with tetrahydrobiopterin (BH₄), the natural cofactor of phenylalanine hydroxylase (PAH), can reduce blood phenylalanine (Phe) levels in patients with BH₄-responsive phenylketonuria (PKU). A number of studies has reported on the short-term BH₄ treatment of patients with PKU, but long-term data are lacking. Here, we describe the effects of long-term treatment with BH₄ on 16 patients, who showed a >28% reduction in blood Phe following testing for BH₄ overload. The mean dose of BH₄ was 16 mg/kg body weight (range 5–36 mg/kg body weight). The mean treatment duration was 56 months (range 24–110 months). Of 16 patients, 14 achieved long-term Phe control with BH₄ treatment, with a mean blood Phe concentration of 321 ± 236 µmol/l. The mean decrease from baseline in blood Phe levels in these 14 patients was 54.6%. Of the seven patients who required continued dietary restriction, Phe intake increased from 200–300 mg/day to 800–1000 mg/day. Factors that may cause fluctuation of Phe levels in BH₄-treated patients include patients’ PAH genotype, Phe intake, changes in protein catabolism or anabolism, and periods of illness or infection.