Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

(often shortened to LCHAD deficiency)
Reviewed July 2009

What is LCHAD deficiency?

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).

Signs and symptoms of LCHAD deficiency typically appear during infancy or early childhood and can include feeding difficulties, lack of energy (lethargy), low blood sugar (hypoglycemia), weak muscle tone (hypotonia), liver problems, and abnormalities in the light-sensitive tissue at the back of the eye (retina). Later in childhood, people with this condition may experience muscle pain, breakdown of muscle tissue, and a loss of sensation in their arms and legs (peripheral neuropathy). Individuals with LCHAD deficiency are also at risk for serious heart problems, breathing difficulties, coma, and sudden death.

Problems related to LCHAD deficiency can be triggered by periods of fasting or by illnesses such as viral infections. 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 LCHAD deficiency?

The incidence of LCHAD deficiency is unknown. One estimate, based on a Finnish population, indicates that 1 in 62,000 pregnancies is affected by this disorder. In the United States, the incidence is probably much lower.

What genes are related to LCHAD deficiency?

Mutations in the HADHA gene cause LCHAD deficiency. The HADHA gene provides instructions for making part of an enzyme complex called mitochondrial trifunctional protein. This enzyme complex functions in mitochondria, the energy-producing centers within cells. As the name suggests, mitochondrial trifunctional protein contains three enzymes that each perform a different function. This enzyme complex is required to break down (metabolize) a group of fats called long-chain fatty acids. Long-chain fatty acids are found in foods such as milk and certain oils. These fatty acids are stored in 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 HADHA gene that cause LCHAD deficiency disrupt one of the functions of this enzyme complex. These mutations prevent the normal processing of long-chain fatty acids from food and body fat. As a result, these fatty acids are not converted to energy, which can lead to some features of this disorder, such as lethargy and hypoglycemia. Long-chain fatty acids or partially metabolized fatty acids may also build up and damage the liver, heart, muscles, and retina. This abnormal buildup causes the other signs and symptoms of LCHAD deficiency.

Related Gene(s)

Changes in this gene are associated with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.

  • HADHA

How do people inherit LCHAD 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 LCHAD deficiency?

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

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/long-chain-l-3-hydroxyacyl-coa-dehydrogenase-deficiency)
  • Genetic Testing Registry: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/CN074230)
  • MedlinePlus Encyclopedia: Hypoglycemia (http://www.nlm.nih.gov/medlineplus/ency/article/000386.htm)
  • MedlinePlus Encyclopedia: Peripheral Neuropathy (http://www.nlm.nih.gov/medlineplus/ency/article/000593.htm)

You might also find information on the diagnosis or management of LCHAD deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/long-chain-3-hydroxyacyl-coa-dehydrogenase-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/long-chain-3-hydroxyacyl-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 LCHAD deficiency?

You may find the following resources about LCHAD 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 LCHAD deficiency?

  • 3-hydroxyacyl-CoA dehydrogenase, long chain, deficiency
  • long-chain 3-hydroxy acyl CoA dehydrogenase deficiency
  • long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
  • long-chain 3-OH acyl-CoA dehydrogenase deficiency
  • trifunctional protein deficiency, type 1

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 LCHAD deficiency?

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

What glossary definitions help with understanding LCHAD deficiency?

acids ; autosomal ; autosomal recessive ; breakdown ; cell ; CoA ; coenzyme A ; coma ; deficiency ; dehydrogenase ; enzyme ; fasting ; fatty acids ; gene ; hypoglycemia ; hypotonia ; incidence ; inherited ; lethargy ; mitochondria ; muscle tone ; neuropathy ; newborn screening ; OH ; oxidation ; peripheral ; peripheral neuropathy ; population ; protein ; recessive ; retina ; screening ; syndrome ; tissue

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

References

  • Angdisen J, Moore VD, Cline JM, Payne RM, Ibdah JA. Mitochondrial trifunctional protein defects: molecular basis and novel therapeutic approaches. Curr Drug Targets Immune Endocr Metabol Disord. 2005 Mar;5(1):27-40. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15777202?dopt=Abstract)
  • den Boer ME, Wanders RJ, Morris AA, IJlst L, Heymans HS, Wijburg FA. Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: clinical presentation and follow-up of 50 patients. Pediatrics. 2002 Jan;109(1):99-104. (http://www.ncbi.nlm.nih.gov/pubmed/11773547?dopt=Abstract)
  • Fahnehjelm KT, Holmström G, Ying L, Haglind CB, Nordenström A, Halldin M, Alm J, Nemeth A, von Döbeln U. Ocular characteristics in 10 children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a cross-sectional study with long-term follow-up. Acta Ophthalmol. 2008 May;86(3):329-37. Epub 2007 Dec 19. Erratum in: Acta Ophthalmol. 2008 Jun;86(4):466. (http://www.ncbi.nlm.nih.gov/pubmed/18162058?dopt=Abstract)
  • Gillingham MB, Purnell JQ, Jordan J, Stadler D, Haqq AM, Harding CO. Effects of higher dietary protein intake on energy balance and metabolic control in children with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency. Mol Genet Metab. 2007 Jan;90(1):64-9. Epub 2006 Sep 22. (http://www.ncbi.nlm.nih.gov/pubmed/16996288?dopt=Abstract)
  • Oey NA, den Boer ME, Wijburg FA, Vekemans M, Augé J, Steiner C, Wanders RJ, Waterham HR, Ruiter JP, Attié-Bitach T. Long-chain fatty acid oxidation during early human development. Pediatr Res. 2005 Jun;57(6):755-9. Epub 2005 Apr 21. (http://www.ncbi.nlm.nih.gov/pubmed/15845636?dopt=Abstract)
  • Rinaldo P, Matern D, Bennett MJ. Fatty acid oxidation disorders. Annu Rev Physiol. 2002;64:477-502. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11826276?dopt=Abstract)
  • Sims HF, Brackett JC, Powell CK, Treem WR, Hale DE, Bennett MJ, Gibson B, Shapiro S, Strauss AW. The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):841-5. (http://www.ncbi.nlm.nih.gov/pubmed/7846063?dopt=Abstract)
  • Spiekerkoetter U, Lindner M, Santer R, Grotzke M, Baumgartner MR, Boehles H, Das A, Haase C, Hennermann JB, Karall D, de Klerk H, Knerr I, Koch HG, Plecko B, Röschinger W, Schwab KO, Scheible D, Wijburg FA, Zschocke J, Mayatepek E, Wendel U. Management and outcome in 75 individuals with long-chain fatty acid oxidation defects: results from a workshop. J Inherit Metab Dis. 2009 Aug;32(4):488-97. doi: 10.1007/s10545-009-1125-9. Epub 2009 Apr 29. (http://www.ncbi.nlm.nih.gov/pubmed/19399638?dopt=Abstract)
  • Tyni T, Paetau A, Strauss AW, Middleton B, Kivelä T. Mitochondrial fatty acid beta-oxidation in the human eye and brain: implications for the retinopathy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Pediatr Res. 2004 Nov;56(5):744-50. Epub 2004 Sep 3. (http://www.ncbi.nlm.nih.gov/pubmed/15347768?dopt=Abstract)
  • Tyni T, Pihko H. Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Acta Paediatr. 1999 Mar;88(3):237-45. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10229030?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: July 2009
Published: October 20, 2014