ACADSB

The ACADSB gene provides instructions for making an enzyme called 2-methylbutyryl-coenzyme A (CoA) dehydrogenase that plays an important role in processing proteins. Normally, the body breaks down proteins from food into smaller parts called amino acids. Amino acids can be further processed to provide energy for growth and development. In cells throughout the body, 2-methylbutyryl-CoA dehydrogenase is found within specialized structures called mitochondria. Mitochondria convert energy from food to a form that cells can use.

The enzyme 2-methylbutyryl-CoA dehydrogenase helps to process a particular amino acid called isoleucine. Specifically, this enzyme helps with the third step in the breakdown of isoleucine. This step is a chemical reaction that converts a molecule called 2-methylbutyryl-CoA to another molecule, tiglyl-CoA. Additional chemical reactions convert tiglyl-CoA into molecules that are used for energy.

2-methylbutyryl-coenzyme A dehydrogenase deficiency - caused by mutations in the ACADSB gene

Researchers have identified several mutations in the ACADSB gene that cause 2-methylbutyryl-coenzyme A dehydrogenase deficiency. Many of these mutations replace one of the amino acids in the 2-methylbutyryl-CoA dehydrogenase enzyme with an incorrect amino acid. Other mutations lead to a smaller version of this enzyme that is missing several amino acids. As a result of these mutations, 2-methylbutyryl-CoA dehydrogenase has little or no activity. With a shortage (deficiency) of this enzyme, the body is unable to break down isoleucine properly. As a result, isoleucine is not converted to energy, which can lead to characteristic features of this disorder, such as lethargy and muscle weakness. Improper processing of isoleucine also allows a substance called 2-methylbutyrylglycine and related compounds to build up to harmful levels, causing serious health problems.