NCBI updates clinical guidance for phenylalanine hydroxylase deficiency
The National Center for Biotechnology Information published an updated GeneReviews entry on phenylalanine hydroxylase deficiency, commonly called phenylketonuria. Authors Arnold and Vockley describe outcomes across a wide spectrum. Early-treated cases show modest decreases in intellectual function and variable impairments in executive function, attention, and fine motor skills, plus increased rates of anxiety and depression. Neurologic problems can include hypertonia, paraplegia, movement disorders, and seizures, though some improve when blood phenylalanine concentration drops. Late-diagnosed or untreated cases cause irreversible intellectual disability, neurobehavioral and psychological issues, motor disturbances, seizures, and microcephaly. The guideline recommends lifelong dietary phenylalanine restriction for all patients with untreated blood phenylalanine above 360 micromoles per liter, confirmed by newborn screening, plasma amino acid analysis, and molecular testing for biallelic PAH pathogenic variants. FDA-approved pharmacologic options include sapropterin dihydrochloride, sepiapterin, and pegvaliase.
The update gives clinicians current protocols for diagnosing and managing newborns and adults with PAH deficiency, including treatment thresholds and approved drug therapies.
Written by the Genomes desk from the primary source cited and linked above and checked against it. Research use only; not medical advice. Corrections: [email protected].