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Genetic and Rare Diseases Information Center (GARD)

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Pyruvate dehydrogenase deficiency

Other Names for this Disease
  • PDHC
  • Pyruvate dehydrogenase complex deficiency
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What causes pyruvate dehydrogenase deficiency?

Pyruvate dehydrogenase (PDH) deficiency is usually caused by a deficiency of one or more enzymes or cofactors (such as thiamine) that are needed for an important chemical reaction in the cells of the body. These enzymes or cofactors are part of the pyruvate dehydrogenase complex and normally convert (or aid in converting) a chemical called pyruvate to another chemical called acetyl-coenzyme A (CoA), which is one of two important chemicals the body needs to make citrate for the cells. Because pyruvate cannot be converted to acetyl-CoA, there is too much pyruvate in the cells, which then gets used to produce more lactic acid (which is toxic in large amounts) and alanine; there is also not enough citrate being made by the body. Citrate is the first step in another important group of chemical reactions called the citric acid cycle, which then cannot proceed. The body tries to make alternate pathways to produce more acetyl-CoA, but there is still not enough energy made in the body, especially in the central nervous system (CNS). The amount of energy that is deficient depends on the amount of the enzyme that is deficient. The condition is sometimes referred to as pyruvate dehydrogenase complex (PDHC) deficiency because there is a "complex" of three enzymes normally used in the reaction; when any one or more of the enzymes needed for the above-described reaction are deficient, the condition results. The most common form of pyruvate dehydrogenase deficiency is caused by mutations in the X-linked dominant E1 alpha gene; all other causes are thought to be due to mutations in recessive genes.[1]
Last updated: 1/4/2011

  1. Richard E Frye, Paul J Benke. Pyruvate dehydrogenase complex deficiency. eMedicine. November 6, 2009; Accessed 1/3/2011.