Conditions · Metabolism: fatty acids and ketones
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency !
An inherited disorder in which the body cannot use fat well for energy; fasting or an infection can cause severe hypoglycaemia.
Updated 2026-11-01
Structures involved
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In biochemistry
- Fatty acid β-oxidation: Step 1 · Acyl-CoA dehydrogenase (VLCAD, MCAD, SCAD by chain length)
- Newborn screening
- Carnitine palmitoyltransferase I (CPT-I)
- Medium-chain acyl-CoA dehydrogenase (MCAD)
- Carnitine (L-carnitine)
- Carnitine shuttle
- Fed, fasting and starvation states
What it is
An autosomal recessive defect of the MCAD enzyme (ACADM gene) that blocks β-oxidation of medium-chain fatty acids. It is the most common fatty acid oxidation disorder.
Who gets it
About 1 in 17,000 births in the United States, more common in northern European ancestry. It is less common in Latin America; in Colombia Law 1980 of 2019 expanded newborn screening and tandem mass spectrometry testing is being rolled out gradually.
Causes
- Pathogenic variants in both copies of ACADM; c.985A>G is the most common in European populations
- Autosomal recessive inheritance: parents are usually healthy carriers
Risk factors
- Prolonged fasting (more than a few hours in infants)
- Infections with fever, vomiting or diarrhoea
- Affected sibling or unexplained sudden death in the family
Pathophysiology
Without MCAD, β-oxidation stops when the chain reaches 6–12 carbons. During fasting the liver gets too little acetyl-CoA: it makes no ketone bodies and gluconeogenesis lacks energy, while tissues burn more glucose. The result is hypoketotic hypoglycaemia. Medium-chain fatty acids and their products (octanoylcarnitine, dicarboxylic acids, hexanoylglycine) build up, are toxic to liver and brain, and cause lethargy, brain oedema and fatty liver.
Symptoms and signs
- Vomiting and poor feeding during an infection
- Drowsiness and lethargy
- Hypotonia
- Seizures
- Hepatomegaly
Diagnosis
- Clinical
- Suspected with hypoketotic hypoglycaemia and lethargy after fasting or illness, or after a positive newborn screen.
- Tests
- Acylcarnitine profile with high octanoylcarnitine (C8) and raised C8/C2 and C8/C10 ratios; urine organic acids with dicarboxylic acids and hexanoylglycine; glucose, ketones, ammonia and transaminases during a crisis; ACADM molecular testing.
- Imaging
- Not needed for diagnosis; ultrasound can show fatty liver and brain MRI can show oedema in severe crises.
Treatment
- Acute
- In a crisis: immediate intravenous glucose to stop lipolysis
- Lifestyle
- Avoid prolonged fasting, with age-appropriate feeding schedules
- Lifestyle
- Written sick-day emergency plan with extra carbohydrate
- Follow-up
- Follow-up by a metabolic disease team
Complications
- Brain damage from hypoglycaemia
- Sudden death in the first crisis
- Intellectual disability or secondary epilepsy
Prognosis
With diagnosis by screening and avoidance of fasting, most children develop normally; an undiagnosed first crisis can be fatal.
Prevention
- Expanded newborn screening and family genetic counselling.
Test yourself
Think of the answer, then tap the question to see it.
Which laboratory finding marks a crisis of MCAD deficiency?
Hypoglycaemia with low ketones (hypoketotic), because without β-oxidation the liver makes no ketone bodies.
Which raised acylcarnitine points to MCAD deficiency on screening?
Octanoylcarnitine (C8).
What is the key measure to prevent crises?
Avoiding prolonged fasting and giving carbohydrate on sick days.
Related conditions
- Primary carnitine deficiency
- Carnitine palmitoyltransferase II (CPT-II) deficiency
- Jamaican vomiting sickness (ackee poisoning)
- Epilepsy and seizures
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Medium-chain acyl-CoA dehydrogenase deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); ACADM gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); mitochondrial fatty acid beta-oxidation of saturated fatty acids (Reactome, 2026).
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