ACADS

The ACADS gene provides instructions for making an enzyme called short-chain acyl-coenzyme A (CoA) dehydrogenase. This enzyme is important for breaking down a group of fats called short-chain fatty acids. These fatty acids are found in some foods and are also created when components of foods, such as fiber, are broken down by bacteria in the intestines. The short-chain acyl-CoA dehydrogenase enzyme is essential for converting these fatty acids into energy. This enzyme functions in mitochondria, the energy-producing centers within cells.

short-chain acyl-coenzyme A dehydrogenase deficiency - caused by mutations in the ACADS gene

Approximately 15 mutations that cause short-chain acyl-CoA dehydrogenase deficiency have been identified. Almost all of these mutations switch an amino acid building block in the ACADS enzyme. These genetic changes prevent the enzyme from properly breaking down and processing short-chain fatty acids. As a result, these fats are not converted into energy, which can lead to the characteristic signs and symptoms of this disorder, including lack of energy (lethargy), low blood sugar (hypoglycemia), poor muscle tone (hypotonia), and weakness.

Researchers have also identified two common variations (polymorphisms) in the ACADS gene that change a single amino acid in the enzyme. Unlike other alterations in the ACADS gene, these polymorphisms do not cause short-chain acyl-CoA dehydrogenase deficiency but may increase a person's risk of developing this disorder. One of these polymorphisms replaces the amino acid arginine with the amino acid tryptophan at protein position 147 (written as Arg147Trp or R147W). The other polymorphism switches the amino acid glycine with the amino acid serine at protein position 185 (written as Gly185Ser or G185S). Other genetic and lifestyle factors likely influence the risk of developing this condition when a person carries either of these polymorphisms.