What is medium-chain acyl-CoA dehydrogenase (MCAD) deficiency?

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a rare genetic metabolic disorder that impairs the breakdown of medium-chain fatty acids, with an incidence of 1 in 10,000 to 1 in 30,000 births.^[1][2] People with MCAD deficiency cannot efficiently metabolize stored fats or ingested MCTs, which leads to insufficient energy during times when large amounts of energy are needed (e.g., during fasting, illness, or prolonged exercise).^[1][2] This energy insufficiency can result in hypoketotic hypoglycemia — low blood sugar without a corresponding rise in ketones.^[1][2]

The MCAD enzyme, essential for beta-oxidation in mitochondria, converts medium-chain fatty acids into acetyl-CoA to produce adenosine triphosphate (ATP) — i.e., energy — in the mitochondria.^[1] A mutation in the ACADM gene prevents the MCAD enzyme from being produced and disrupts beta-oxidation, which potentially causes severe complications such as developmental delays, brain damage, organ failure, or death.^[1] Early detection through newborn screening and dietary management can prevent these outcomes.^[1] Treatment includes avoiding prolonged fasting, consuming high-carbohydrate, low-fat meals, and increasing the carbohydrate intake during illness.^[1] Dietary supplementation with L-carnitine is sometimes used, though its use is controversial because its efficacy remains unclear.^{[1][3][4][5][6][7]}