The pyruvate dehydrogenase complex converts pyruvate into acetyl-CoA. The complex is made up of multiple copies of several enzymes called E1, E2, and E3. The E1 enzyme is made up of 4 subunits; two called E1 alpha and two called E1 beta. Mutations in the gene that makes E1 alpha, the PDHA1 gene account for 80% of cases of pyruvate dehydrogenase deficiency.
Excess pyrvate is converted into lactic acid, resulting in lactic acidosis.
Patients with Lon Peptidase 1 (LONP1) mutations can also have pyruvate dehydrogenase deficiencies. Mutations in the LONP1 gene can also result in CODAS (Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies) syndrome.