A 4-month-old infant presents with progressive developmental delay, hypotonia, microcephaly, and complex seizures. Newborn screening for PKU was normal. Plasma phenylalanine is normal. Urine pterin analysis shows decreased biopterin and increased neopterin. Which enzyme is deficient?

• A Phenylalanine hydroxylase
• B Dihydropteridine reductase
• C GTP cyclohydrolase I
• D 6-Pyruvoyltetrahydropterin synthase ✓

Explanation

Normal phenylalanine with neurological deterioration and a low biopterin-to-neopterin ratio points to a BH4 synthesis defect, not a recycling defect. 6-Pyruvoyltetrahydropterin synthase (PTPS) deficiency raises neopterin and lowers biopterin. DHPR deficiency shows elevated biopterin. GTP cyclohydrolase I deficiency lowers both biopterin and neopterin. These disorders require neurotransmitter replacement, not just phenylalanine restriction.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.