Summary
The mammalian pyruvate dehydrogenase complex (PDHC) catalyses the oxidative and irreversible decarboxylation of pyruvate, giving acetyl-CoA, Co2, and NADH + H+. It is located in the mitochondrial inner membrane-matrix space. It plays an essential role in aerobic energy metabolism by controlling the supply of acetyl-CoA arising from carbohydrates and amino acids which are oxidised or converted to fat.
PDHC deficiencies primarily affect the nervous system and are associated with congenital lactic acidosis. The clinical presentation is highly heterogeneous, varying from mild episodic ataxia to severe, rapidly fatal lactic acidosis. The most frequent forms include developmental delay, mental retardation, lactic acidosis and cerebral abnormalities leading to death in early infancy. The most frequent PDHC deficiencies are due to a defect of the Elα subunit. Other defects are very rare and do not differ clinically from the PDH-Elα defects. Fifty-two different mutations have been found in both sexes in the Elα-gene located on the X-chromosome. In girls, due to the variable inactivation of this chromosome in different tissues, the biochemical expression of the deficiency may be difficult to interpret. A lot of mutations are sporadic and most are not found in the mother’s somatic cells. We report here an overview of all mutations described in the literature up until now.
Keywords
- Lactic Acidosis
- Pyruvate Dehydrogenase
- Pyruvate Dehydrogenase Complex
- Dihydrolipoamide Dehydrogenase
- Lactic Acidemia
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Marsac, C., François, D., Fouque, F., Benelli, C. (1999). Pyruvate Dehydrogenase Deficiencies. In: Lestienne, P. (eds) Mitochondrial Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59884-5_13
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DOI: https://doi.org/10.1007/978-3-642-59884-5_13
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