2.1. Pyruvate dehydrogenase deficiency

Mutations in the PDHB gene are a very rare cause of pyruvate dehydrogenase deficiency. This condition is characterized by a potentially life-threatening buildup of a chemical called lactic acid in the body (lactic acidosis), delayed development, and neurological problems. These mutations change single protein building blocks (amino acids) in the E1 beta protein, resulting in an abnormal E1 beta protein that cannot function properly. The abnormal protein may not be able to interact with E1 alpha to form the E1 enzyme or with other factors needed for the E1 enzyme to perform its chemical reaction. A decrease of functional E1 beta leads to a reduction of pyruvate dehydrogenase complex activity. With decreased function of this complex, pyruvate builds up and is converted, in another chemical reaction, to lactic acid, causing lactic acidosis. In addition, the production of cellular energy is diminished. The brain, which is especially dependent on this form of energy, is severely affected, resulting in the neurological problems associated with pyruvate dehydrogenase deficiency.

2.2. Leigh syndrome