A newborn screen in India is positive for elevated phenylalanine (850 µmol/L, reference <120 µmol/L). Urine pterins show markedly reduced biopterin. A dihydropteridine reductase (DHPR) assay is normal. Which form of hyperphenylalaninemia does this most likely represent, and what is the critical addition to treatment beyond a low-phenylalanine diet?
- A Classic PKU; treat with sapropterin (BH4) alone
- B DHPR deficiency; treat with BH4 and folinic acid
- C BH4 synthesis defect (GTP cyclohydrolase or 6-PTS deficiency); supplement with BH4 and neurotransmitter precursors (L-DOPA, 5-HTP) ✓
- D Transient neonatal hyperphenylalaninemia; no treatment required
Explanation
BH4 (tetrahydrobiopterin) is a cofactor for phenylalanine hydroxylase. Defects in BH4 synthesis (GTP cyclohydrolase I deficiency or 6-pyruvoyltetrahydropterin synthase deficiency) cause hyperphenylalaninemia and, crucially, deficient synthesis of neurotransmitters serotonin and dopamine (because BH4 is also required for tryptophan and tyrosine hydroxylases). These patients develop severe neurological deterioration despite controlling phenylalanine, because neurotransmitter deficiency persists. Treatment requires BH4 supplementation PLUS L-DOPA/carbidopa and 5-hydroxytryptophan to restore neurotransmitter levels. Reduced urinary biopterin with normal DHPR differentiates this from DHPR deficiency.
Reference: Ghai Essential Pediatrics, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.