A term neonate becomes lethargic and hypotonic on day 3 with myoclonic seizures, hiccups, and apnoea requiring ventilation. Septic screen is negative. Plasma ammonia is mildly raised at 110 micromol/L. Plasma alanine is elevated and plasma glycine is 1200 micromol/L (normal <400). Cerebrospinal fluid/plasma glycine ratio is 0.25. CSF lactate and organic acids are normal. The most likely diagnosis is:

• A Propionic acidaemia
• B Pyridoxine-dependent epilepsy
• C Ornithine transcarbamylase deficiency
• D Non-ketotic hyperglycinaemia ✓

Explanation

Non-ketotic hyperglycinaemia results from a defect in the mitochondrial glycine cleavage system, causing massive glycine accumulation. Glycine acts as an excitatory neurotransmitter in cortex, explaining intractable myoclonic seizures, hiccups, and apnoea. The diagnostic hallmark is an elevated CSF-to-plasma glycine ratio above 0.08, with normal organic acids and lactate, distinguishing it from propionic and methylmalonic acidaemias where organic acids are abnormal and ketosis occurs. Ammonia is normal or only mildly elevated, unlike urea cycle defects.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.