ACADM

The ACADM gene provides instructions for making an enzyme called medium-chain acyl-coenzyme A (CoA) dehydrogenase that is important for converting certain fats to energy. 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. Fatty acid oxidation is particularly important during periods without food (fasting) or when energy demands are increased.

Medium-chain acyl-CoA dehydrogenase is required for the step in fatty acid oxidation that metabolizes a group of fats called medium-chain fatty acids. These fatty acids are found in foods such as milk and certain oils, are stored in the body's fat tissue, and are produced when larger fatty acids are metabolized.

Medium-chain acyl-CoA dehydrogenase functions within mitochondria, the energy-producing centers in cells. This enzyme is found in mitochondria of several types of tissues, particularly the liver.

medium-chain acyl-coenzyme A dehydrogenase deficiency - caused by mutations in the ACADM gene

More than 40 ACADM gene mutations that cause medium-chain acyl-coenzyme A dehydrogenase deficiency have been identified. Many of these mutations change one of the building blocks (amino acids) used to make the medium-chain acyl-CoA dehydrogenase 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 medium-chain acyl-CoA dehydrogenase, medium-chain fatty acids are not metabolized properly. As a result, these fats are not converted to energy, which can lead to signs and symptoms of this disorder such as lack of energy (lethargy) and low blood sugar. Medium-chain fatty acids or partially metabolized fatty acids may accumulate in tissues and can damage the liver and brain, causing serious complications.