A 2-week-old neonate on newborn screening is found to have elevated blood phenylalanine (18 mg/dL). Urinary pterins show elevated biopterin with low neopterin. Dihydropteridine reductase (DHPR) activity is normal. BH4 loading test shows >30% reduction in phenylalanine. This biochemical profile is consistent with:
- A Classic phenylketonuria (PAH deficiency)
- B BH4 deficiency due to GTP cyclohydrolase I deficiency
- C Tyrosinemia type I causing secondary hyperphenylalaninemia
- D BH4-responsive mild PKU, treatable with sapropterin ✓
Explanation
A positive BH4 loading test (>30% fall in phenylalanine at 8 hours) combined with normal DHPR activity and elevated biopterin indicates BH4-responsive hyperphenylalaninemia or BH4-responsive PKU. These patients have residual PAH activity that is allosterically stimulated by exogenous BH4. Sapropterin (synthetic BH4, Kuvan) can replace or supplement dietary phenylalanine restriction in these children. Classic PKU shows no response to BH4. GTP cyclohydrolase I deficiency would show low biopterin AND low neopterin. DHPR deficiency would show normal biopterin with elevated hydroxylated pterins.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.