ACADS

The ACADS gene provides instructions for making an enzyme called short-chain acyl-CoA dehydrogenase (SCAD). This enzyme functions within mitochondria, the energy-producing centers within cells. SCAD is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them to energy.

SCAD is required to metabolize a group of fats called short-chain fatty acids. These fatty acids are found in some foods and are also 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.

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

More than 40 mutations in the ACADS gene have been found to cause short-chain acyl-CoA dehydrogenase (SCAD) deficiency. Almost all of these mutations change single protein building blocks (amino acids) in the SCAD enzyme. These mutations prevent the enzyme from properly metabolizing 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 each change one amino acid in the SCAD enzyme. Unlike other changes in the ACADS gene, these polymorphisms do not cause SCAD 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 environmental factors likely influence the risk of developing SCAD deficiency when a person carries either of these polymorphisms.