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Genetics Home Reference: your guide to understanding genetic conditions
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Very long-chain acyl-CoA dehydrogenase deficiency

(often shortened to VLCAD deficiency)
Reviewed November 2009

What is VLCAD deficiency?

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).

Signs and symptoms of VLCAD deficiency typically appear during infancy or early childhood and can include low blood sugar (hypoglycemia), lack of energy (lethargy), and muscle weakness. Affected individuals are also at risk for serious complications such as liver abnormalities and life-threatening heart problems. When symptoms begin in adolescence or adulthood, they tend to be milder and usually do not involve the heart.

Problems related to VLCAD deficiency can be triggered by periods of fasting, illness, and exercise. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

How common is VLCAD deficiency?

VLCAD deficiency is estimated to affect 1 in 40,000 to 120,000 people.

What genes are related to VLCAD deficiency?

Mutations in the ACADVL gene cause VLCAD deficiency. This gene provides instructions for making an enzyme called very long-chain acyl-CoA dehydrogenase, which is required to break down (metabolize) a group of fats called very long-chain fatty acids. These fatty acids are found in foods and the body's fat tissues. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.

Mutations in the ACADVL gene lead to a shortage (deficiency) of the VLCAD enzyme within cells. Without sufficient amounts of this enzyme, very long-chain fatty acids are not metabolized properly. As a result, these fats are not converted to energy, which can lead to the characteristic signs and symptoms of this disorder such as lethargy and hypoglycemia. Very long-chain fatty acids or partially metabolized fatty acids may also build up in tissues and damage the heart, liver, and muscles. This abnormal buildup causes the other signs and symptoms of VLCAD deficiency.

Related Gene(s)

Changes in this gene are associated with very long-chain acyl-CoA dehydrogenase deficiency.

  • ACADVL

How do people inherit VLCAD deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of VLCAD deficiency?

These resources address the diagnosis or management of VLCAD deficiency and may include treatment providers.

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/very-long-chain-acyl-coa-dehydrogenase-deficiency)
  • Gene Review: Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK6816)
  • Genetic Testing Registry: Very long chain acyl-CoA dehydrogenase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0342784)
  • MedlinePlus Encyclopedia: Newborn Screening Tests (http://www.nlm.nih.gov/medlineplus/ency/article/007257.htm)

You might also find information on the diagnosis or management of VLCAD deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about VLCAD deficiency?

You may find the following resources about VLCAD deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for VLCAD deficiency?

  • ACADVL
  • acyl-CoA dehydrogenase very long chain deficiency
  • very long-chain acyl coenzyme A dehydrogenase deficiency
  • very long-chain acyl-coenzyme A dehydrogenase deficiency
  • VLCAD-C
  • VLCAD-H

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about VLCAD deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding VLCAD deficiency?

acids ; autosomal ; autosomal recessive ; cell ; CoA ; coenzyme A ; deficiency ; dehydrogenase ; enzyme ; fasting ; fatty acids ; gene ; hypoglycemia ; inherited ; lethargy ; newborn screening ; oxidation ; recessive ; screening ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Andresen BS, Bross P, Vianey-Saban C, Divry P, Zabot MT, Roe CR, Nada MA, Byskov A, Kruse TA, Neve S, Kristiansen K, Knudsen I, Corydon MJ, Gregersen N. Cloning and characterization of human very-long-chain acyl-CoA dehydrogenase cDNA, chromosomal assignment of the gene and identification in four patients of nine different mutations within the VLCAD gene. Hum Mol Genet. 1996 Apr;5(4):461-72. Erratum in: Hum Mol Genet 1996 Sep;5(9):1390. (http://www.ncbi.nlm.nih.gov/pubmed/8845838?dopt=Abstract)
  • Gregersen N, Andresen BS, Corydon MJ, Corydon TJ, Olsen RK, Bolund L, Bross P. Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype-phenotype relationship. Hum Mutat. 2001 Sep;18(3):169-89. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11524729?dopt=Abstract)
  • Laforêt P, Acquaviva-Bourdain C, Rigal O, Brivet M, Penisson-Besnier I, Chabrol B, Chaigne D, Boespflug-Tanguy O, Laroche C, Bedat-Millet AL, Behin A, Delevaux I, Lombès A, Andresen BS, Eymard B, Vianey-Saban C. Diagnostic assessment and long-term follow-up of 13 patients with Very Long-Chain Acyl-Coenzyme A dehydrogenase (VLCAD) deficiency. Neuromuscul Disord. 2009 May;19(5):324-9. doi: 10.1016/j.nmd.2009.02.007. Epub 2009 Mar 26. (http://www.ncbi.nlm.nih.gov/pubmed/19327992?dopt=Abstract)
  • Mathur A, Sims HF, Gopalakrishnan D, Gibson B, Rinaldo P, Vockley J, Hug G, Strauss AW. Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death. Circulation. 1999 Mar 16;99(10):1337-43. (http://www.ncbi.nlm.nih.gov/pubmed/10077518?dopt=Abstract)
  • Parini R, Menni F, Garavaglia B, Fesslova V, Melotti D, Massone ML, Lamantea E, Rimoldi M, Vizziello P, Gatti R. Acute, severe cardiomyopathy as main symptom of late-onset very long-chain acyl-coenzyme A dehydrogenase deficiency. Eur J Pediatr. 1998 Dec;157(12):992-5. (http://www.ncbi.nlm.nih.gov/pubmed/9877038?dopt=Abstract)
  • Spiekerkoetter U, Sun B, Zytkovicz T, Wanders R, Strauss AW, Wendel U. MS/MS-based newborn and family screening detects asymptomatic patients with very-long-chain acyl-CoA dehydrogenase deficiency. J Pediatr. 2003 Sep;143(3):335-42. (http://www.ncbi.nlm.nih.gov/pubmed/14517516?dopt=Abstract)
  • Strauss AW, Powell CK, Hale DE, Anderson MM, Ahuja A, Brackett JC, Sims HF. Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10496-500. (http://www.ncbi.nlm.nih.gov/pubmed/7479827?dopt=Abstract)
  • Touma EH, Rashed MS, Vianey-Saban C, Sakr A, Divry P, Gregersen N, Andresen BS. A severe genotype with favourable outcome in very long chain acyl-CoA dehydrogenase deficiency. Arch Dis Child. 2001 Jan;84(1):58-60. (http://www.ncbi.nlm.nih.gov/pubmed/11124787?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2009
Published: November 24, 2014