A term neonate develops myoclonic seizures on day 3 with profound hypotonia and apnea. Plasma ammonia is normal, there is no acidosis or ketosis, and plasma glycine is 1400 micromol/L with a CSF-to-plasma glycine ratio above 0.08. The defective enzyme complex is:

• A Sarcosine dehydrogenase
• B Serine dehydratase
• C Glycine amidinotransferase
• D Glycine cleavage system ✓

Explanation

Nonketotic hyperglycinemia results from deficiency of the mitochondrial glycine cleavage system (P, H, T, L proteins), which needs pyridoxal phosphate, lipoamide, FAD and tetrahydrofolate. Glycine accumulates in plasma and CSF, acting as an excitatory neurotransmitter at NMDA receptors, causing neonatal seizures and hypotonia. Normal ammonia and absent ketosis exclude organic acidemias, and the CSF-to-plasma ratio above 0.08 supports the diagnosis.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.