Phenylketonuria (PKU)
Inborn Error of Amino Acid Metabolism
Primary risk age: Neonates (Screened at birth; symptoms develop over the first year if untreated)
- Urgency
- Severe
- Typical age
- Neonates (Screened at birth; symptoms develop over the first year if untreated)
- Body system
- Endocrine & Metabolic
Typical course: This is a lifelong genetic metabolic disorder requiring continuous daily dietary management.
Reviewed against AAP · CDC · WHO · NHS guidance Last reviewed 2026-06-13
1. Summary & Pathophysiology
Inborn Error of Amino Acid Metabolism
Pathophysiology (Development Path)
The enzyme deficiency prevents the conversion of the essential amino acid phenylalanine to tyrosine. Phenylalanine accumulates in the blood and tissues, crossing the blood-brain barrier. High brain concentrations are neurotoxic, impairing myelination and neurotransmitter synthesis.
Primary Causes & Etiology
An autosomal recessive mutation in the PAH gene on chromosome 12, leading to a deficiency of the hepatic enzyme phenylalanine hydroxylase.
2. Symptom Continuum
- Early Onset Signs
Asymptomatic at birth. Within the first few months, infants may exhibit vomiting, irritability, and a characteristic "musty" or "mousy" odor to the urine and skin.
- Progressive Phase
Eczema-like skin rashes, fair skin and blue eyes (due to impaired melanin synthesis from tyrosine deficiency), and microcephaly.
- Severe Indicators
Untreated children show severe intellectual disability, autistic-like behaviors, hyperactivity, tremors, and seizures.
3. Clinical Verification
Newborn screening demonstrating elevated blood phenylalanine levels ($ge 2 ext{ mg/dL}$). Diagnosis is confirmed by measuring blood phenylalanine-to-tyrosine ratios.
4. Care & Elements Plan
Primary Care Treatment Plan
Initiate a lifetime dietary restriction of phenylalanine. This requires avoiding high-protein foods and using a specialized phenylalanine-free amino acid medical formula. Maintain blood levels within a target therapeutic range.
Home Support Elements
Maintain a strict low-phenylalanine diet. Weigh foods carefully, monitor intake using dietary logs, and ensure regular blood spot testing at home.
Generic Active Ingredients (No Brands)
- Sapropterin dihydrochloride (generic active cofactor used to enhance remaining enzyme activity in responsive patients)
- Phenylalanine-free amino acid formula.
Lists active elements only. Never administer self-designed therapies.
5. Doctor Critical Lines
Critical Thresholds: When to See a Doctor
Immediate consultation is required if newborn screening indicates elevated phenylalanine levels, or if an infant develops a musty odor or developmental delay.
6. Vaccine & Prevention
Routine Prophylaxis (Prevention)
Pre-conception genetic screening for carrier parents. Strict dietary control for mothers with PKU during pregnancy (maternal PKU) to prevent fetal brain damage.
Immunization Context
No specific immunizations are associated with this metabolic disorder.
7. Timelines & Outlook
Active Timeline
This is a lifelong genetic metabolic disorder requiring continuous daily dietary management.
Expected Prognosis
Excellent if a strict diet is initiated in the first weeks of life. Late initiation leads to irreversible intellectual impairment.
Potential Untreated Complications
Severe intellectual disability, microcephaly, developmental delay, and neurological problems (seizures, tremors).
More in Inherited Inborn Errors of Metabolism
Emergency Classic Galactosemia
Inborn Error of Carbohydrate Metabolism
Neonates (Symptoms present within days of initiating milk feeding)
Emergency Addison's Disease (Adrenal Insufficiency)
Pediatric Primary Adrenal Insufficiency Syndrome
School-aged children and adolescents (rare in infants, though congenital forms exist)
Emergency Congenital Adrenal Hyperplasia (CAH)
Inherited Adrenal Steroidogenesis Enzyme Deficiency
Neonates and infants (salt-wasting crises present in the first 2 weeks of life)