BCKDHB

The BCKDHB gene provides instructions for making one part, the beta subunit, of an enzyme complex (a group of enzymes that work together). This complex is called branched-chain alpha-keto acid dehydrogenase, or BCKD. Two beta subunits connect with two alpha subunits, which are produced from the BCKDHA gene, to form a critical part of the enzyme complex called the E1 component.

The BCKD enzyme complex is responsible for one step in the normal breakdown of three protein building blocks (amino acids). These amino acids—leucine, isoleucine, and valine—are obtained from the diet. They are present in many kinds of food, particularly protein-rich foods such as milk, meat, and eggs. The BCKD enzyme complex is active in mitochondria, which are specialized structures inside cells that serve as energy-producing centers. The breakdown of leucine, isoleucine, and valine produces molecules that can be used for energy.

maple syrup urine disease - caused by mutations in the BCKDHB gene

More than 40 mutations in the BCKDHB gene have been identified in people with maple syrup urine disease, most often in individuals with the severe, classic form of the disorder. Some of these mutations change single amino acids in the beta subunit of the BCKD enzyme complex. A particular mutation is most common in people of Ashkenazi (eastern and central European) Jewish descent; this mutation replaces the amino acid arginine with the amino acid proline at position 183 in the beta subunit (written as Arg183Pro or R183P). Other BCKDHB mutations insert or delete small amounts of DNA in the gene.

Mutations in the BCKDHB gene disrupt the normal function of the BCKD enzyme complex, preventing it from effectively breaking down leucine, isoleucine, and valine. As a result, these amino acids and their byproducts build up in the body. This accumulation is toxic to cells and tissues, particularly in the nervous system. The buildup of these substances can lead to seizures, developmental delay, and the other medical problems associated with maple syrup urine disease.