DLD

The DLD gene provides instructions for making a protein called dihydrolipoamide dehydrogenase. This protein is part of several enzyme complexes (groups of enzymes that work together). These complexes are essential for the breakdown of certain molecules to produce energy in cells. Dihydrolipoamide dehydrogenase forms a subunit called the E3 component that is shared by several enzyme complexes.

Branched-chain alpha-keto acid dehydrogenase, or BCKD, is one of the enzyme complexes that include the E3 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 breakdown of these amino acids produces molecules that can be used for energy.

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

More than 10 mutations in the DLD gene have been identified in people with maple syrup urine disease. Mutations in this gene are responsible for a variant form of the disorder that includes lactic acidosis, a potentially life-threatening complication caused by the buildup of lactic acid in the body's tissues.

Most DLD mutations change single amino acids in the E3 component of the BCKD enzyme complex. These mutations alter the structure of the E3 component, which prevents the enzyme complex from effectively breaking down valine, isovaline, and leucine. 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.