PDP1

Pyruvate dehydrogenase deficiency

At least one mutation in the PDP1 gene has been identified in individuals with pyruvate dehydrogenase deficiency; mutation of the PDP1 gene is a very rare cause of this condition. Pyruvate dehydrogenase deficiency is characterized by a potentially life-threatening buildup of a chemical called lactic acid in the body (lactic acidosis), delayed development, and neurological problems.

The identified mutation removes one protein building block (amino acid) of the pyruvate dehydrogenase phosphatase 1 protein, which is thought to change its shape. The abnormal protein cannot remove the phosphate group from the pyruvate dehydrogenase complex, which reduces the activity of the complex. With decreased activity 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.