Sepiapterin approved for children and adults with phenylketonuria (PKU): A therapeutics bulletin of the American College of Medical Genetics and Genomics (ACMG)

Phenylketonuria (PKU), also known as phenylalanine hydroxylase (PAH) (HGNC:8582) deficiency, is an autosomal recessive disorder of phenylalanine (Phe) metabolism due to deficiency of the enzyme PAH, which normally converts Phe to tyrosine (Tyr) (HGNC:12442) in the presence of the cofactor tetrahydrobiopterin (BH4).1 Deficient PAH activity results in elevated blood and brain Phe concentrations, resulting in profound neurocognitive delays if left untreated. PKU represents a spectrum of disease severity correlating to residual enzyme activity, from mild hyperphenylalaninemia to classic PKU, the most severe form.