A term neonate develops lethargy, hypotonia, seizures, and hiccups after 48 hours of feeding. Ammonia is normal, there is no acidosis, and plasma lactate is unremarkable. EEG shows burst suppression. CSF glycine is 600 micromol/L with a CSF-to-plasma glycine ratio of 0.15. The defective enzyme complex is:
- A Branched-chain alpha-ketoacid dehydrogenase
- B Serine dehydratase
- C Glycine cleavage system ✓
- D Methionine adenosyltransferase
Correct answer: C. Glycine cleavage system
Explanation
Nonketotic hyperglycinemia arises from deficiency of the mitochondrial glycine cleavage enzyme system (P, T, H, L protein components), producing elevated glycine in plasma and CSF. A CSF-to-plasma glycine ratio above 0.08 supports the diagnosis. The absence of ketoacidosis distinguishes it from maple syrup urine disease, where branched-chain ketoacid dehydrogenase is defective, killing option A. Normal ammonia excludes urea cycle defects. Burst suppression EEG with intractable hiccups is characteristic.
Reference: Nelson Textbook of Pediatrics, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.