The use of sapropterin to lower phenylalanine concentration in blood in people with phenylketonuria.

Phenylketonuria occurs due to an inherited deficiency of the enzyme phenylalanine hydroxylase. If untreated it causes an excessive accumulation of the amino acid phenylalanine in the body which prevents normal brain development. The established treatment for phenylketonuria consists of dietary restriction of natural protein but with prescribed phenylalanine-free amino acid, mineral and vitamin supplements. With this treatment the long-term outcome for people with phenylketonuria is excellent but the diet is onerous. Sapropterin dihydrochloride, the cofactor for phenylalanine hydroxylase, could lower phenylalanine concentration significantly in phenylketonuria and might allow a relaxation of dietary restrictions. The review identified two trials of sapropterin dihydrochloride; one in children and adults with no restricted diet and one in just children whose diet was restricted. The trials used different doses of sapropterin dihydrochloride (10 mg/kg/day and 20 mg/kg/day). We could not combine any data due to different formats of presentation. We found evidence to show that some people with mild or moderate phenylketonuria can benefit from the use of sapropterin dihydrochloride in the short term; the concentration of blood phenylalanine was lowered after treatment in both trials. The trial with the higher dose also measured the outcome change in protein tolerance. It reported an increase in protein tolerance in response to sapropterin. There were no adverse effects associated with the use of sapropterin dihydrochloride in the short term. We found no evidence on the effects of long-term treatment. We could not draw any conclusions on its benefits in severe phenylketonuria.