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# 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

Tap one to see what it is and open it in 3D.

- [Liver](https://durgical.com/en/anatomy/liver/)
- [White matter](https://durgical.com/en/anatomy/white-matter-of-telencephalon/)
- [Kidneys](https://durgical.com/en/anatomy/kidney/)

## In biochemistry

- [Fatty acid β-oxidation: Step 1 · Acyl-CoA dehydrogenase (VLCAD, MCAD, SCAD by chain length)](https://durgical.com/en/biochemistry/pathways/fatty-acid-oxidation/#paso-1)
- [Newborn screening](https://durgical.com/en/biochemistry/topics/newborn-screening/)
- [Carnitine palmitoyltransferase I (CPT-I)](https://durgical.com/en/biochemistry/enzymes/carnitine-palmitoyltransferase-i/)
- [Medium-chain acyl-CoA dehydrogenase (MCAD)](https://durgical.com/en/biochemistry/enzymes/medium-chain-acyl-coa-dehydrogenase/)
- [Carnitine (L-carnitine)](https://durgical.com/en/biochemistry/molecules/carnitine/)
- [Carnitine shuttle](https://durgical.com/en/biochemistry/topics/carnitine-shuttle/)
- [Fed, fasting and starvation states](https://durgical.com/en/biochemistry/topics/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

## Red flags

- Lethargy or coma in an infant who is fasting or ill
- Hypoglycaemia with low or absent ketones
- Seizures with low glucose
- Family history of sudden infant death

## 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](https://durgical.com/en/anatomy/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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/conditions/medium-chain-acyl-coa-dehydrogenase-deficiency/)

## Related conditions

- [Primary carnitine deficiency](https://durgical.com/en/conditions/primary-carnitine-deficiency/)
- [Carnitine palmitoyltransferase II (CPT-II) deficiency](https://durgical.com/en/conditions/carnitine-palmitoyltransferase-ii-deficiency/)
- [Jamaican vomiting sickness (ackee poisoning)](https://durgical.com/en/conditions/jamaican-vomiting-sickness/)
- [Epilepsy and seizures](https://durgical.com/en/conditions/epilepsy-and-seizures/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Medium-chain acyl-CoA dehydrogenase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/medium-chain-acyl-coa-dehydrogenase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [ACADM gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/acadm/) (MedlinePlus, US National Library of Medicine, 2026); [mitochondrial fatty acid beta-oxidation of saturated fatty acids](https://reactome.org/PathwayBrowser/#/R-HSA-77286) (Reactome, 2026).

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Source: https://durgical.com/en/conditions/medium-chain-acyl-coa-dehydrogenase-deficiency/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/medium-chain-acyl-coa-dehydrogenase-deficiency/