ACADVL

The ACADVL gene provides instructions for making an enzyme called very long-chain acyl-coenzyme A (CoA) dehydrogenase that is important for converting 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.

Very long-chain acyl-CoA dehydrogenase is required for the step in fatty acid oxidation that metabolizes a group of fats called very long-chain fatty acids. These fatty acids are found in foods such as milk and certain oils, and they are also stored in the body's fat tissue.

Very long-chain acyl-CoA dehydrogenase functions within mitochondria, the energy-producing centers in cells. This enzyme is abundant in the heart and certain muscles, where it plays a key role in supplying energy. Significant levels of this enzyme are also found in liver mitochondria, and much smaller amounts are found in other tissues.

very long-chain acyl-coenzyme A dehydrogenase deficiency - caused by mutations in the ACADVL gene

Researchers have identified more than 90 mutations in the ACADVL gene that cause very long-chain acyl-coenzyme A dehydrogenase deficiency. Many of these mutations delete one of the building blocks (amino acids) used to make very long-chain acyl-CoA dehydrogenase or improperly substitute one amino acid for another amino acid in the enzyme. These mutations alter the enzyme's structure, severely reducing or eliminating its activity. Other mutations delete part of the ACADVL gene or create a premature stop signal in the instructions for making very long-chain acyl-CoA dehydrogenase. As a result, very little functional enzyme is produced.

With a shortage (deficiency) of functional very long-chain acyl-CoA dehydrogenase, very-long 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 the lack of energy (lethargy) and low blood sugar (hypoglycemia). Very long-chain fatty acids or partially metabolized fatty acids may accumulate in tissues and can damage the heart, liver, and muscles, causing serious complications.