Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
Reviewed May 2006
What is long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency?
Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting). Normally, through a process called fatty acid oxidation, several enzymes work in a step-wise fashion to break down (metabolize) fats and convert them to energy. People with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency have inadequate levels of an enzyme required for a step that metabolizes a group of fats called long-chain fatty acids.
Typically, initial signs and symptoms of this disorder occur during infancy or early childhood and can include feeding difficulties, lack of energy (lethargy), low blood sugar (hypoglycemia), muscle weakness (hypotonia), liver problems, and abnormalities in the part of the eye that detects light and color (the retina). Muscle pain, breakdown of muscle tissue, and abnormalities in the nervous system that affect arms and legs (peripheral neuropathy) may occur later in childhood. Individuals with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency are also at risk for complications such as life-threatening heart and breathing problems, coma, and sudden unexpected death.
Problems related to long-chain 3-hydroxyacyl-coenzyme A dehydrogenase 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 long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency?
The incidence of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase 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 long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency?
Mutations in the HADHA gene cause long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency.
Mutations in the HADHA gene lead to inadequate levels of an enzyme called long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase, which is part of a protein complex known as mitochondrial trifunctional protein. Long-chain fatty acids from food and body fat cannot be metabolized and processed without sufficient levels of this enzyme. As a result, these fatty acids are not converted to energy, which can lead to characteristic features of this disorder, such as lethargy and hypoglycemia. Long-chain fatty acids or partially metabolized fatty acids may build up in tissues and damage the liver, heart, retina, and muscles, causing more serious complications.
How do people inherit long-chain 3-hydroxyacyl-coenzyme A dehydrogenase 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 treatment for long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency?
You may find information on treatment or management of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency or some of its symptoms in the links below, particularly the links for
Educational resources and Patient support.
Where can I find additional information about long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency?
You may find the following resources about long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency helpful. These materials are written for the general public.
- MedlinePlus - Health information
- Health Topic: Metabolic Disorders (http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html)
- Health Topic: Newborn Screening (http://www.nlm.nih.gov/medlineplus/newbornscreening.html)
- Educational resources - Information pages
- Illinois Department of Public Health (http://www.idph.state.il.us/HealthWellness/fs/mcad.htm)
- Iowa Department of Public Health (http://www.idph.state.ia.us/genetics/common/pdf/lchad.pdf)
- Oregon Department of Human Services (http://oregon.gov/DHS/ph/nbs/docs/lchad.pdf)
- Orphanet (http://www.orpha.net//consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=5)
- Screening, Technology, and Research in Genetics (http://www.newbornscreening.info/Parents/fattyaciddisorders/LCHADD.html)
- State of Missouri Department of Health and Senior Services (http://www.dhss.mo.gov/NewbornScreening/3hydroxy-hexadecanoyldisorders.pdf)
- Patient support - For patients and families
- Children Living with Inherited Metabolic Diseases (CLIMB) (http://www.climb.org.uk)
- Fatty Oxidation Disorders (FOD) Family Support Group (http://www.fodsupport.org/lchad.htm)
- Save Babies Through Screening Foundation (http://www.savebabies.org/diseasedescriptions/lchad.php)
- United Mitochondrial Disease Foundation (http://www.umdf.org/)
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency?
- 3-hydroxyacyl-CoA dehydrogenase, long chain, deficiency
- LCHAD deficiency
- long-chain 3-hydroxy acyl CoA dehydrogenase deficiency
- long-chain 3-OH acyl-CoA dehydrogenase deficiency
- trifunctional protein deficiency, type 1
See 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 long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency?
- See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
- Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
- Submit your question to Ask the Geneticist (http://www.askthegen.org/).
What glossary definitions help with understanding long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency?
acids ;
autosomal ;
autosomal recessive ;
cell ;
CoA ;
coenzyme A ;
coma ;
complication ;
deficiency ;
dehydrogenase ;
enzyme ;
fasting ;
fatty acids ;
gene ;
hypoglycemia ;
hypotonia ;
incidence ;
infection ;
lethargy ;
mutation ;
nervous system ;
neuropathy ;
newborn screening ;
OH ;
oxidation ;
peripheral ;
peripheral neuropathy ;
population ;
protein ;
recessive ;
retina ;
screening ;
sign ;
symptom ;
syndrome ;
tissue
You may find definitions for these and many other terms in the Genetics Home Reference
Glossary (http://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/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15777202)
- 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/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11773547)
- Rinaldo P, Matern D, Bennett MJ. Fatty acid oxidation disorders. Annu Rev Physiol. 2002;64:477-502. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11826276)
- Scriver, Charles R; The metabolic & molecular bases of inherited disease; 8th ed.; New York : McGraw-Hill, c2001. p2297-2326.
- 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/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=7846063)
- Tyni T, Paetau A, Strauss AW, Middleton B, Kivela 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 03. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15347768)
- 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/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10229030)
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.
|
Indicates a page outside Genetics Home Reference.