|http://ghr.nlm.nih.gov/ A service of the U.S. National Library of Medicine®|
The official name of this gene is “pyruvate dehydrogenase (lipoamide) alpha 1.”
PDHA1 is the gene's official symbol. The PDHA1 gene is also known by other names, listed below.
The PDHA1 gene provides instructions for making a protein called E1 alpha. The E1 alpha protein is a piece (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.
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. These mutations have been divided into two groups. One group includes mutations that add or remove DNA building blocks (nucleotides) to the PDHA1 gene (called insertion and deletion mutations, respectively). These types of mutations occur more commonly in affected females than males. The other group includes mutations that change single protein building blocks (amino acids) in the E1 alpha protein or result in a premature stop signal in the instructions for making the protein (called missense and nonsense mutations, respectively). These types of mutations occur in affected males more often than females.
Mutations in the PDHA1 gene associated with pyruvate dehydrogenase deficiency lead to a reduction in the amount of E1 alpha protein or result in an abnormal protein that cannot function properly. The abnormal protein may not be able to interact with E1 beta to form the E1 enzyme or with other factors needed for the E1 enzyme to perform its chemical reaction. A decrease in functional E1 alpha results in reduced 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.
Cytogenetic Location: Xp22.1
Molecular Location on the X chromosome: base pairs 19,343,892 to 19,361,706
The PDHA1 gene is located on the short (p) arm of the X chromosome at position 22.1.
More precisely, the PDHA1 gene is located from base pair 19,343,892 to base pair 19,361,706 on the X chromosome.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about PDHA1 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
acidosis ; acids ; adenosine triphosphate ; ATP ; cell ; CoA ; deficiency ; dehydrogenase ; deletion ; DNA ; enzyme ; gene ; insertion ; lactic acid ; lactic acidosis ; molecule ; neurological ; protein ; subunit ; syndrome
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.