Last updated 2mo ago
A newborn has an elevated phenylalanine on newborn screening. Without treatment, affected children develop intellectual disability, seizures, and musty body odor.
AR; PAH (phenylalanine hydroxylase)
- Untreated: Severe ID, seizures, eczema, light pigmentation, musty odor
- Newborn screening: Universal (on RUSP)
- Maternal PKU: Microcephaly, CHD, ID in offspring if mother's Phe uncontrolled
- Newborn screening (universal, on RUSP): elevated phenylalanine and elevated Phe/tyrosine ratio
- Confirmatory plasma amino acids: elevated phenylalanine with normal/low tyrosine
- Exclude BH4 (tetrahydrobiopterin) cofactor defects (pterin analysis, dihydropteridine reductase assay), which present similarly but need different treatment
- PAH molecular testing confirms classic PKU and predicts BH4 responsiveness
- Phenylalanine-restricted diet (lifelong), sapropterin (BH4 cofactor) for responsive patients, pegvaliase
"Mousy/musty odor": the characteristic body odor of untreated PKU. Phenylalanine accumulates because it cannot be converted to tyrosine.
Avoid aspartame: aspartame (artificial sweetener) is metabolized to phenylalanine. PKU patients must also avoid high-protein foods.
Tyrosine becomes essential: since PAH (phenylalanine hydroxylase) normally converts Phe to Tyr, tyrosine becomes an essential amino acid in PKU. Decreased tyrosine explains the light skin/hair (less melanin). BH4 (tetrahydrobiopterin) is the cofactor; sapropterin is synthetic BH4.