Disease Directory Phenylketonuria
Metabolic

Phenylketonuria

Also known as: PKU, Phenylalanine hydroxylase deficiency

Prevalence

1 in 10,000–15,000 live births (varies by population)

Onset

Congenital (detected at birth via newborn screening)

Type

Disease

Gene

PAH

About Phenylketonuria

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by mutations in the PAH gene encoding phenylalanine hydroxylase. Without treatment, phenylalanine accumulates and causes irreversible intellectual disability. Early detection via newborn screening and lifelong low-phenylalanine diet, now supplemented by sapropterin (Kuvan) for BH4-responsive patients and pegvaliase (Palynziq) for adults, has transformed outcomes. Clinical trials are exploring gene therapy, mRNA therapy, and next-generation enzyme substitution strategies.

Common Clinical Features

Intellectual disability (if untreated) Seizures Behavioural difficulties Musty or mouse-like odour (from phenylacetate) Fair skin and hair Eczema-like rash Mood disorders in adults Cognitive decline without dietary adherence

Clinical Trial Eligibility Tips

What to know before applying to Phenylketonuria trials.

BH4 responsiveness testing (sapropterin loading test) is key — around 50% of PKU patients are responsive and can significantly relax dietary restrictions.

Trials for gene and mRNA therapy now target adults with PKU who have established disease — eligibility typically requires baseline phenylalanine levels above 600 µmol/L.

Register with the US PKU Registry or European PKU Registry — researchers actively recruit participants from these databases.

Patient Resources

Patient Organization

National PKU Alliance

Visit website ↗

Natural History Registry

US PKU Registry

Join registry ↗

Orphanet

European reference resource for rare diseases

View on Orphanet ↗

NORD

National Organization for Rare Disorders

Search NORD ↗

Find recruiting Phenylketonuria trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for Phenylketonuria. Updated daily.

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