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MBBS QUESTION #10361
Question 1
A neonate with a urea cycle enzyme deficiency (e.g., ornithine transcarbamylase deficiency) develops hyperammonemia with lethargy and encephalopathy. Elevated ammonia is particularly toxic to the brain primarily because it:
  • Depletes cerebral alpha-ketoglutarate (by driving its conversion to glutamate and then glutamine to detoxify ammonia), impairing citric acid cycle function and cellular energy (ATP) production in neurons and astrocytes✔️
  • Directly destroys myelin sheaths via an entirely unrelated, ammonia-specific mechanism
  • Has no established biochemical mechanism of neurotoxicity
  • Selectively affects only peripheral nerves, sparing the central nervous system entirely
Correct Answer Explanation
Astrocytes attempt to detoxify excess ammonia by converting glutamate to glutamine (via glutamine synthetase), a reaction that consumes alpha-ketoglutarate-derived glutamate and depletes citric acid cycle intermediates, impairing neuronal ATP production and contributing to the cerebral edema and encephalopathy characteristic of hyperammonemia.