PDHA1 gene

The PDHA1 gene provides instructions for making a protein that is essential for converting food into energy within the body's cells.

Normal Function

The PDHA1 gene provides instructions for making a protein called E1 alpha. The E1 alpha protein is a subunit of a larger protein: two E1 alpha proteins combine with two copies of another protein called E1 beta (produced from the PDHB gene) to form the E1 enzyme. This enzyme, also known as pyruvate dehydrogenase, is a component of a group of proteins called the pyruvate dehydrogenase complex.

The pyruvate dehydrogenase complex plays an important role in the pathways that convert the energy from food into a form that cells can use. This complex converts a molecule called pyruvate, which is formed from the breakdown of carbohydrates, into another molecule called acetyl-CoA. The E1 enzyme performs one part of this chemical reaction. The conversion of pyruvate is essential to begin the series of chemical reactions that produces adenosine triphosphate (ATP), the cell's main energy source.

Health Conditions Related to Genetic Changes

Pyruvate dehydrogenase deficiency

Mutations in the PDHA1 gene are the most common cause of pyruvate dehydrogenase deficiency, accounting for approximately 80 percent of cases 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.

Dozens of PDHA1 gene mutations have been identified in affected individuals, which are divided into two groups:

• Insertion and deletion mutations: These mutations add or remove DNA building blocks (nucleotides) and occur more commonly in affected females than males.
• Missense and nonsense mutations: These mutations change single protein building blocks (amino acids) or result in a premature stop signal in the instructions for making the protein. These occur in affected males more often than females.

Mutations in the PDHA1 gene lead to a reduction in the amount of E1 alpha protein or result in an abnormal protein that cannot function properly. This results in reduced pyruvate dehydrogenase complex activity. With decreased function, pyruvate builds up and is converted 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 the condition.

Leigh syndrome

MedlinePlus Genetics provides information about Leigh syndrome.

Other Names for This Gene

• ODPA_HUMAN
• PDHA
• PDHCE1A
• PDHE1-A type I
• PHE1A
• pyruvate dehydrogenase (lipoamide) alpha 1
• pyruvate dehydrogenase alpha 1
• pyruvate dehydrogenase complex, E1-alpha polypeptide 1
• pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial