Phenylketonuria is an inherited autosomal recessive disorder in which the enzyme phenylalanine hydroxylase does not work, so phenylalanine builds up and damages the developing brain. Newborn screening finds it early, and a lifelong low-phenylalanine diet prevents most harm.
Key symptoms
- Normal at birth; problems appear over months if untreated
- Developmental delay and intellectual disability if untreated
- Musty or mousy body odor
- Eczema and light skin and hair
- Seizures, behavior problems or attention issues
What you find on exam
- Growth, head circumference and development
- Skin for eczema and light pigmentation
- Neurologic exam
- Review of diet and formula adherence
Tests
- Newborn screening blood spot for high phenylalanine
- Confirm with plasma amino acids (phenylalanine and tyrosine)
- Check for BH4 cofactor defects
- Regular blood phenylalanine levels to guide the diet
Treatment basics
- Start as early as possible, ideally in the first 1 to 2 weeks of life
- Lifelong low-phenylalanine diet with a special medical formula
- Avoid aspartame and high-protein foods
- Sapropterin for patients who respond; pegvaliase for some adults
- Tight control before and during pregnancy to prevent birth defects
Red flags
- Abnormal newborn screen without follow-up
- Developmental regression or seizures
- Pregnancy in a woman with PKU and high levels
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Sources: NCCPA PANCE Content Blueprint; NBOME COMLEX-USA clinical presentations; AAMC Core Entrustable Professional Activities (Core EPAs). Written by Making Synapses. Making Synapses is not affiliated with these organizations.