A 6-year-old boy presents with episodes of hypoketotic hypoglycaemia after overnight fasting, hepatomegaly, and proximal muscle weakness. Plasma acylcarnitine profile shows long-chain acylcarnitines. The underlying defect is impaired:

• A Glycogen debranching enzyme activity
• B Transport of long-chain fatty acids across the inner mitochondrial membrane ✓
• C Conversion of acetyl-CoA to acetoacetate in hepatocytes
• D Uptake of free fatty acids into adipocytes

Explanation

Carnitine shuttle defects impair entry of long-chain acyl-CoA into mitochondria via CPT-I, translocase, and CPT-II, blocking hepatic beta-oxidation and ketogenesis during fasting. The result is hypoketotic hypoglycaemia with raised long-chain acylcarnitines. Option A describes Cori disease, which produces fasting hypoglycaemia but with lactic acidosis and normal ketones, not long-chain acylcarnitinaemia. Option C describes a synthetic defect such as HMG-CoA synthase deficiency rather than a transport defect.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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