New era in treatment for phenylketonuria: Pharmacologic therapy with sapropterin dihydrochloride

Abstract

Oral administration of sapropterin hydrochloride, recently approved for use by the US Food and Drug Administration and the European Commission, is a novel approach for the treatment of phenylketonuria (PKU), one of the most common inborn errors of metabolism. PKU is caused by an inherited deficiency of the enzyme phenylalanine hydroxylase (PAH), and the pathophysiology of the disorder is related to chronic accumulation of the free amino acid phenylalanine in tissues. Contemporary therapy is based upon restriction of dietary protein intake, which leads to reduction of blood phenylalanine levels. This therapy is difficult to maintain throughout life, and dietary noncompliance is commonplace. Sapropterin dihydrochloride is a synthetic version of tetrahydrobiopterin, the naturally occurring pterin cofactor that is required for PAH-mediated phenylalanine hydroxylation. In a subset of individuals with PAH deficiency, sapropterin administration leads to reduction in blood phenylalanine levels independent of dietary protein. For these individuals, sapropterin is an effective novel therapy for PKU.