A term neonate has recurrent apnea, hiccups, hypotonia, and myoclonic seizures beginning on day 3. Imaging shows a thin corpus callosum. Plasma and cerebrospinal fluid glycine levels are markedly elevated, and the CSF-to-plasma glycine ratio exceeds 0.08. Which enzyme complex is defective?
- A Serine hydroxymethyltransferase
- B Glycine cleavage system ✓
- C D-amino acid oxidase
- D Glycine amidinotransferase
Correct answer: B. Glycine cleavage system
Explanation
Nonketotic hyperglycinemia results from deficiency of the mitochondrial glycine cleavage system (P, H, T, L proteins). Glycine accumulates and acts as an excitatory neurotransmitter at NMDA receptors and glycinergic synapses, producing hiccups, seizures, and hypotonia. B CSF-to-plasma glycine ratio above 0.08 confirms the diagnosis. Serine hydroxymethyltransferase deficiency causes serine-related defects without this glycine pattern, and D-amino acid oxidase is unrelated to glycine clearance in humans.
Reference: Nelson Textbook of Pediatrics, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.