Sapropterin. Phenylketonuria: for a minority of patients.

Phenylketonuria and tetrahydrobiopterin deficiency are rare congenital disorders involving phenylalanine metabolism. If left untreated, they lead to severe mental retardation and neuropsychological problems. Management is based on a diet low in phenylalanine, started as early as possible. Sapropterin is a synthetic analogue of tetrahydrobiopterin, a cofactor for the enzyme that metabolises phenylalanine into tyrosine. Sapropterin is authorised in the European Union for some patients with phenylketonuria or tetrahydrobiopterin deficiency. In patients with phenylketonuria, the clinical evaluation of sapropterin is based on two randomised placebo-controlled trials lasting 6 to 10 weeks. One trial included 133 "responders" (about 20% of the patients initially enrolled). No data on clinical complications or better acceptance of the diet were reported. In the second placebo-controlled trial, 45 "responders" (about half of the children initially enrolled) aged 4 to 12 years who were on a low-phenylalanine diet were able to tolerate an increase in phenylalanine (dry powder) supplementation when treated with sapropterin. In late 2009, the clinical evaluation of sapropterin in tetrahydrobiopterin deficiency was based on non-comparative data in about forty patients, showing a decline in phenylalanine concentrations. No signs of serious adverse effects have emerged so far. Sapropterin has not been studied in pregnant women, but animal data call for caution. In summary, sapropterin seems to make it possible to relax some dietary restrictions in a minority of children with phenylketonuria (moderate relaxation of dietary control, on average). No data are available on the impact of sapropterin on clinical complications. Evaluation is inadequate in patients with tetrahydrobiopterin deficiency and a register should be established for all treated patients.