Phenylketonuria therapy reference (2026)

Phenylketonuria therapy in 2026 organises around several modalities, applied across age and severity.

Low-phenylalanine diet plus medical formula: foundational therapy across all PKU patients. Strict early-life dietary control prevents the cognitive and developmental consequences of phenylalanine accumulation; lifelong dietary control is the modern recommendation, as relaxed diet in adolescence and adulthood is associated with neurocognitive consequences.

Sapropterin (BH4): an oral medicine that increases residual PAH enzyme activity in BH4-responsive patients. A trial of sapropterin identifies responders. Sapropterin is used as an adjunct to dietary therapy and can allow some liberalisation of diet.

Pegvaliase: a pegylated enzyme that converts phenylalanine to a non-toxic metabolite, given by subcutaneous injection. Approved in adults with elevated phenylalanine despite other therapy. Requires careful initiation due to hypersensitivity risk; with appropriate dose escalation and monitoring, can substantially reduce phenylalanine levels and allow protein-liberalised diet.

Emerging modalities: AAV gene therapy delivering a working PAH gene is reaching pivotal data. mRNA-based protein replacement programs are in earlier-stage trials.

Newborn screening. PKU is one of the original conditions on newborn screening panels and remains universally screened in most jurisdictions.

The care-pathway question matters. Adolescent and adult PKU care has historically been less structured than paediatric care, with poor adherence to dietary therapy in many adults. Modern care emphasises lifelong dietary therapy supported by adult metabolic clinics.