Foundations · Year 1 · from Foundations
Case 2: Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency
Clinical Image
Source: Wikipedia - Medium-chain acyl-CoA dehydrogenase deficiency - CC BY-SA 3.0
Case Presentation
A 9-month-old infant is brought to the emergency department after being found unresponsive. He had mild upper respiratory symptoms for 2 days and decreased oral intake. Prior to this, he was a healthy, normally developing child. On examination, he is hypotonic and poorly responsive. Blood glucose is critically low at 25 mg/dL. Surprisingly, serum ketones are inappropriately low (hypoketotic hypoglycemia). Liver function tests show mild transaminase elevation. He is immediately given IV dextrose with rapid improvement in mental status. Given the presentation of hypoketotic hypoglycemia triggered by fasting during illness, a fatty acid oxidation disorder is suspected. Newborn screening results are retrieved and show elevated C8 (octanoylcarnitine) on his blood spot, which had been flagged but the family was not contacted. Confirmatory testing shows elevated medium-chain acylcarnitines and reduced MCAD enzyme activity. Genetic testing confirms homozygous mutations in ACADM. The family is extensively counseled on avoidance of fasting, emergency protocols during illness (cornstarch, frequent feeding, early IV dextrose), and wearing a medical alert bracelet. With proper management, prognosis is excellent.
Key Learning Points
- MCAD deficiency is the most common inherited fatty acid oxidation disorder; affected individuals cannot complete beta-oxidation of medium-chain fatty acids, blocking ketone body production during fasting
- Hypoketotic hypoglycemia is the hallmark: during fasting, glucose falls as hepatic glycogen is depleted, but ketones fail to rise because beta-oxidation is blocked, leaving the brain without alternative fuel
- Elevated octanoylcarnitine (C8) on acylcarnitine profile is diagnostic; MCAD deficiency is included in newborn screening programs because early diagnosis and fasting avoidance prevent life-threatening episodes