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Medium chain acyl-CoA dehydrogenase deficiency

Synonym(s) ACADM deficiency
Carnitine deficiency secondary to medium-chain acyl-CoA dehydrogenase deficiency
MCAD deficiency
Prevalence 1-9 / 100 000
Inheritance Autosomal recessive
Age of onset Infancy
  • E71.3
  • C0220710
  • C536038
MedDRA -


Disease definition

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is an inborn error of mitochondrial fatty acid oxidation characterized by a rapidly progressive metabolic crisis, often presenting as hypoketotic hypoglycemia, lethargy, vomiting, seizures and coma, which can be fatal in the absence of emergency medical intervention.


The estimated birth prevalence of MCADD is thought to range from 1/4,900 to 1/27,000 in Caucasian populations and is highest in individuals of Northern European descent. The worldwide birth prevalence is 1/14,600.

Clinical description

MCADD usually presents 3 to 24 months after birth in previously healthy infants. However, neonatal presentations are well described as are those in adults, given sufficient metabolic stress (such as significant alcohol ingestion). Nevertheless, many affected individuals remain asymptomatic throughout life. Typically hypoketotic hypoglycemia, lethargy and vomiting are triggered by an infection, fasting or surgery. Some patients, however, can present with a progressive metabolic crisis despite ketosis and normal blood glucose. Rarely patients may present in crisis with ''paradoxically'' gross ketosis. During a crisis, a patient may manifest with lethargy, emesis, respiratory arrest, seizures, hepatomegaly and rapid progression to cardiac arrest unless emergency treatment is implemented. Potential brain injury occurring during these episodes can lead to an increased risk of long term neurological damage. Sudden unexplained death can sometimes be the first manifestation of this disease. Historically, about 25% of undiagnosed patients die during their first presentation of a crisis.


MCADD is caused by mutations in the ACADMgene (1p31) which encodes the mitochondrial MCAD protein. The most prevalent mutation, c.985A>G, (K329E), p.(Lys329Glu), accounted for about 80% of clinical disease prior to newborn screening programs but many more individuals are now being identified with other ACADM mutations.

Diagnostic methods

Diagnosis is through the identification of a characteristic abnormal pattern in dried blood spots or plasma of acylcarnitines species (increased C6, C8 and increased ratio of C8/C10 with abnormal urine organic acid findings of C6 to C10 dicarboxylic acids, hexanoylglycine and suberylglycine). Final confirmation is by mutation analysis. MCADD is now included in newborn screening programs in many European countries such as the UK, Germany, the Netherlands, Portugal and Spain.

Differential diagnosis

Differential diagnosis includes other disorders of mitochondrial fatty acid oxidation including multiple acyl-CoA dehydrogenase deficiency (MADD) (see this term).

Genetic counseling

MCADD is inherited autosomal recessively. Genetic counseling is possible.

Management and treatment

Strict avoidance of fasting is the primary objective. Medium chain triglycerides should be avoided but no other special dietary restrictions are required. Guidelines are available for the safe interval time between feeds for infants and young children. The use of low dose carnitine supplementation in patients who develop a low blood carnitine status remains controversial. In symptomatic patients, simple carbohydrates are given by mouth (glucose tablets) or intravenously until blood glucose level is maintained at above 5 mmol/L. During intercurrent infections, an emergency regimen should be made available. Immediate medical attention is needed in case of decompensation. Artificial sweeteners should be avoided.


The prognosis is excellent in diagnosed patients who avoid fasting and who are managed appropriately during an intercurrent illness/ metabolic crisis.

Expert reviewer(s)

  • Dr Simon OLPIN

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