The ACADM gene provides instructions for making an enzyme called medium-chain acyl-CoA dehydrogenase (MCAD). This enzyme functions within mitochondria, the energy-producing centers in cells. MCAD is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them to energy.
MCAD is required to metabolize a group of fats called medium-chain fatty acids. These fatty acids are found in foods and body fat and are produced when larger fatty acids are metabolized. Fatty acids are a major source of energy for the heart and muscles. During periods without food (fasting), fatty acids are also an important energy source for the liver and other tissues.
Health Conditions Related to Genetic Changes
Medium-chain acyl-CoA dehydrogenase deficiency
More than 80 mutations in the ACADM gene have been found to cause medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. Many of these mutations change single protein building blocks (amino acids) in the MCAD enzyme. The most common change replaces the amino acid lysine with the amino acid glutamic acid at position 304 in the enzyme (written as Lys304Glu or K304E). This mutation and other amino acid substitutions alter the enzyme's structure, severely reducing or eliminating its activity. Other types of mutations lead to an abnormally small and unstable enzyme that cannot function.
With a shortage (deficiency) of functional MCAD enzyme, medium-chain fatty acids are not metabolized properly. As a result, these fats are not converted to energy, which can lead to some features of this disorder such as lack of energy (lethargy) and low blood sugar (hypoglycemia). Medium-chain fatty acids or partially metabolized fatty acids may build up in tissues and damage the liver and brain. This abnormal buildup causes the other signs and symptoms of MCAD deficiency.More About This Health Condition
Other Names for This Gene
- acyl-CoA dehydrogenase, C-4 to C-12 straight chain
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- 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. Citation on PubMed
- Hsu HW, Zytkovicz TH, Comeau AM, Strauss AW, Marsden D, Shih VE, Grady GF, Eaton RB. Spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by newborn screening. Pediatrics. 2008 May;121(5):e1108-14. doi: 10.1542/peds.2007-1993. Citation on PubMed
- Maier EM, Gersting SW, Kemter KF, Jank JM, Reindl M, Messing DD, Truger MS, Sommerhoff CP, Muntau AC. Protein misfolding is the molecular mechanism underlying MCADD identified in newborn screening. Hum Mol Genet. 2009 May 1;18(9):1612-23. doi: 10.1093/hmg/ddp079. Epub 2009 Feb 18. Citation on PubMed or Free article on PubMed Central
- Maier EM, Liebl B, Röschinger W, Nennstiel-Ratzel U, Fingerhut R, Olgemöller B, Busch U, Krone N, v Kries R, Roscher AA. Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency. Hum Mutat. 2005 May;25(5):443-52. Citation on PubMed
- Waddell L, Wiley V, Carpenter K, Bennetts B, Angel L, Andresen BS, Wilcken B. Medium-chain acyl-CoA dehydrogenase deficiency: genotype-biochemical phenotype correlations. Mol Genet Metab. 2006 Jan;87(1):32-9. Epub 2005 Nov 15. Citation on PubMed
- Wang SS, Fernhoff PM, Hannon WH, Khoury MJ. Medium chain acyl-CoA dehydrogenase deficiency human genome epidemiology review. Genet Med. 1999 Nov-Dec;1(7):332-9. Citation on PubMed