Clinical Medicine Insights: Therapeutics

Phenylketonuria (PKU) is an autosomal recessive disorder related to a deficiency in the enzyme phenylalanine hydroxylase (PAH), which converts phenylalanine to tyrosine. As a result, phenylalanine can accumulate in the bloodstream, potentially leading to severe neurologic sequelae. Traditionally, PKU management involves strict dietary phenylalanine restriction, although adherence to this diet is suboptimal, necessitating improved therapeutic options.

Sapropterin (Kuvan®) is a synthetic form of tetrahydrobioterin (BH4), a cofactor for PAH, and offers promise for patients with residual enzyme production. In four pivotal phase 2 and 3 trials, as well as several smaller trials, sapropterin has demonstrated significantly improved plasma phenylalanine concentrations in patients with BH4-responsive PKU. Furthermore, data exist to support reduced dependence on a restricted phenylalanine diet. Sapropterin has a favorable safety profile, but further studies are warranted to evaluate its long-term effects.

Sapropterin represents a significant advancement in PKU management, and its clinical role may continue to evolve as more data become available and clinicians gain experience with this novel pharmacologic agent.