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Medium-chain acyl-CoA dehydrogenase deficiency (MCADD)

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A previously healthy 14-month-old becomes unresponsive after an overnight fast during a viral illness. Labs show hypoketotic hypoglycemia.

AR; ACADM

  • Common variant: c.985A>G (K329E) - ~80% of alleles
  • Most common FAO disorder
  • Hypoketotic hypoglycemia (inappropriately low ketones)
  • Hepatomegaly, elevated liver enzymes during crisis
  • Risk of sudden death, particularly in infancy.
  • On RUSP
  • Newborn screening (acylcarnitine profile): elevated C8 (octanoylcarnitine), with elevated C8/C10 ratio
  • During crisis: hypoketotic hypoglycemia, elevated medium-chain dicarboxylic acids on urine organic acids
  • Confirmatory testing: molecular analysis of ACADM (common c.985A>G allele) and/or enzyme activity assay
  • Avoid fasting, emergency protocol during illness

NBS: High C8: on newborn screening acylcarnitine profile, elevated C8 (octanoylcarnitine) is the key marker for MCADD.

Hypo-ketotic hypoglycemia: MCADD cannot break down medium-chain fats to make ketone bodies, so during fasting, glucose is used up without ketone backup. "Defective beta oxidation of fats, can't generate acetyl-CoA from fat, so no ketone bodies."

MCAD mnemonic: "MCAD Macaque". Treatment is to avoid fasting, symptoms include decreased glucose (fatigue, sweating), defect in C6-C10 fatty acid oxidation
MCAD mnemonic: "MCAD Macaque". Treatment is to avoid fasting, symptoms include decreased glucose (fatigue, sweating), defect in C6-C10 fatty acid oxidation

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