A newborn's newborn screening (NBS) card shows elevated phenylalanine of 22 mg/dL. Confirmatory plasma amino acid chromatography confirms phenylketonuria (PKU). Which tetrahydrobiopterin (BH4) loading test finding would suggest BH4-responsive PKU, making sapropterin dihydrochloride a treatment option?
- A Phenylalanine falls by <10% at 24 hours
- B Phenylalanine falls by ≥30% within 24 hours of BH4 loading ✓
- C Urine pterins show elevated neopterin only
- D Phenylalanine rises transiently then returns to baseline
Explanation
BH4-responsive PKU is identified by the BH4 loading test: administration of sapropterin (BH4) at 20 mg/kg/day and monitoring plasma phenylalanine. A decrease in phenylalanine of ≥30% from baseline (some guidelines use >30%, others >20%) within 24–48 hours indicates responsiveness, meaning the residual PAH enzyme activity can be pharmacologically enhanced with BH4 supplementation. This is seen in milder PAH mutations with some residual activity. Non-responsive PKU (null PAH mutations) requires strict phenylalanine-restricted diet alone. Elevated neopterin alone without elevated biopterin suggests GTP cyclohydrolase deficiency, a BH4 biosynthesis defect.
Reference: Ghai Essential Pediatrics, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.