Recombinant phenylalanine ammonia lyase in phenylketonuria

摘要

If untreated, patients with phenylketonuria show severe intellectual impairment, seizures, microcephaly, and growth failure, biochemically associated with hyperphenylalaninaemia. Important milestones in the history of phenylketonuria have been the biochemical identification of affected patients in 1934, development of dietary treatment in 1953, introduction of a population screening test for asymptomatic neonates in 1964, and introduction of the first medical treatment, sapropterin, in 1999. Even with sapropterin, which relieves the burden of strict dietary treatment, especially in patients with milder forms of phenylketonuria, dietary treatment remains the keystone of management. However, the restriction of natural protein, and hence phenylalanine, in the diet is onerous and compliance is difficult to achieve. Moreover, even with strict adherence to dietary management, the outcome is not optimal.