MCAD Deficiency

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Synonyms: medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, ACADM deficiency

This is an autosomal recessive inherited disorder of fatty acid metabolism, caused by a mutation of the medium-chain acyl-CoA dehydrogenase gene (ACADM) on chromosome 1. The gene has been mapped to locus 1p31; several allelic variations have been reported. The most common mutation is called G985.[1] This is because of a substitution of a guanine for an adenine nucleotide at the 985th residue.

Save time & improve your PDP on

  • Notes Add notes to any clinical page and create a reflective diary
  • Track Automatically track and log every page you have viewed
  • Print Print and export a summary to use in your appraisal
Click to find out more »

Fatty acids are unable to be metabolised beyond the medium-chain size (8-12 carbon stage), and gluconeogenesis is effectively inhibited. In response to any fasting or metabolic stress (eg illness) the body is unable to metabolise fat (so no ketones are produced), and continues to metabolise glucose producing hypoglycaemia.[2] The clinical result is severe hypoglycaemia and hypoketonuria, with accumulation of monocarboxylic fatty acids and dicarboxylic organic acids.

Incidence: 1:8,000 to 1:15,000 births.[1] There is an equal gender predisposition.

  • Age at presentation is quite variable.
  • It most commonly presents in infants aged >3 months, when overnight feeds reduce in frequency. The gap between feeds is then long enough for acute hypoglycaemia to occur, producing symptoms of preprandial irritability, drowsiness, jitteriness, sweating, coma and seizures.
  • It can present as sudden death in adults. There is a 25% mortality rate in undiagnosed cases.[3]
  • It can present with:
  • In later childhood it may present with episodic hypoglycaemia, eg with sweating, collapse, confusion, or developmental delay.
  • It has been reported presenting after a first episode of alcohol intoxication.[4]
  • It very occasionally presents in adulthood with muscle weakness and fatigue.
  • Survivors of acute episodes may have severe hypoglycaemia-induced brain damage.

These may be normal in between attacks.

  • Acutely - hypoglycaemia.
  • U&E may show high or low bicarbonate and reduced anion gap.
  • LFTs may show elevated enzymes, low plasma carnitine.
  • Urine - medium-chain dicarboxylic aciduria and absent ketones.

Skin biopsy can be performed to confirm diagnosis of primary carnitine deficiency - demonstrating reduced carnitine transport in fibroblasts. Fibroblasts may be used for fatty acid oxidation studies or enzyme assay.

  • Avoidance of fasting. A maximum duration of fasting in children with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency of:
    • Between 6 months and 1 year of age - 8 hours.
    • In the second year of life - 10 hours.
    • Thereafter - 12 hours.[5]
    • There are no firm guidelines on the duration of fasting during situations of intercurrent illness, especially with fever.
  • Because the fundamental biochemical defect is in fatty acid oxidation, the composition of the diet should be adjusted to provide greater calories in carbohydrates and proteins, while minimising lipids.
  • Daily carnitine has been suggested by some specialists; this allows conjugation and excretion of toxic biproducts of blocked fatty acid metabolism. Supplementation may promote clearance of accumulating acylcarnitines during exercise, but there is no apparent beneficial effect on clinical and biochemical indices.[6][7]
  • Genetic counselling should be provided for family members.
  • The heterozygous state is quite common. Testing for the gene should be offered to first-degree relatives of an affected child.
  • Frequent episodes of severe hypoglycaemia carry a risk of adverse effects in the CNS.
  • Hypoglycaemia and hyperammonaemia may cause cerebral oedema and prolonged coma.
  • Prognosis is difficult to predict because of the broad clinical spectrum.
  • The majority of children do well, if appropriately treated.

This is technically possible by demonstrating a marked reduction in octanoate oxidation in cultured amniotic cells obtained via amniocentesis.[8]

The Department of Health introduced routine medium-chain acyl-CoA dehydrogenase (MCAD) deficiency screening in the neonatal blood spot from February 2009.[9]

Further reading & references

  1. Roth KS; Medium-Chain Acyl-CoA Dehydrogenase Deficiency, eMedicine, Sep 2009
  2. Acyl-CoA Dehydrogenase, medium-chain, deficiency of, ACADMD; Online Mendelian Inheritance in Man (OMIM)
  3. Scaglia F; Carnitine Deficiency, eMedicine, Apr 2010
  4. Mayell SJ, Edwards L, Reynolds FE, et al; Late presentation of medium-chain acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2006 Nov 30;.
  5. Derks TG, van Spronsen FJ, Rake JP, et al; Safe and unsafe duration of fasting for children with MCAD deficiency. Eur J Pediatr. 2007 Jan;166(1):5-11. Epub 2006 Jun 21.
  6. Lee PJ, Harrison EL, Jones MG, et al; L-carnitine and exercise tolerance in medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency: a pilot study. J Inherit Metab Dis. 2005;28(2):141-52.
  7. Huidekoper HH, Schneider J, Westphal T, et al; Prolonged moderate-intensity exercise without and with L-carnitine supplementation in patients with MCAD deficiency. J Inherit Metab Dis. 2006 Oct;29(5):631-6. Epub 2006 Aug 2.
  8. Bennett MJ, Allison F, Lowther GW, et al; Prenatal diagnosis of medium-chain acyl-coenzyme A dehydrogenase deficiency. Prenat Diagn. 1987 Feb;7(2):135-41.
  9. NHS Newborn Bloodspot Screening Programme

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Hayley Willacy
Current Version:
Last Checked:
Document ID:
2438 (v23)