Which metabolic disorder presents with hypoketotic hypoglycemia and accumulation of medium-chain fatty-acyl carnitines?

• A. MCAD deficiency
• B. VLCAD deficiency
• C. CPT II deficiency
• D. Pompe disease

Answer: (A)

When fatty acids can’t be fully oxidized in beta-oxidation, the body can’t produce ketone bodies during fasting, so glucose becomes the main fuel and ketones stay low—this is hypoketotic hypoglycemia. In medium-chain acyl-CoA dehydrogenase deficiency, the block is specifically at metabolizing medium-chain fatty acids. As a result, during illness or prolonged fasting, medium-chain fatty acids accumulate and are shunted to form medium-chain acylcarnitines, which appear elevated in the blood. This pattern—recurrent hypoglycemia with low ketone levels and increased medium-chain acylcarnitines—is classic for MCAD deficiency. Clinically, infants may present with vomiting, lethargy, and confusion after fasting or minor illness, and management focuses on avoiding fasting and providing prompt glucose during illness to prevent metabolic crisis.

VLCAD deficiency would more often show accumulation of long-chain acylcarnitines and affects long-chain fatty acids; CPT II deficiency typically presents with muscle weakness and rhabdomyolysis, especially with exercise, and Pompe disease is a glycogen storage disorder with cardiomyopathy and systemic weakness rather than a primary fatty acid oxidation issue.