Pyruvate dehydrogenase deficiency

Overview
Pyruvate Dehydrogenase Deficiency (PDHA) is a human genetic disease. It follows a sex-linked, dominant inheritance pattern, but is approximately equally prevalent in both males and females. It affects a gene which codes for a critical enzyme complex, the Pyruvate dehydrogenase complex (PDC) which links the metabolic pathways of glycolysis and the citric acid cycle by transforming pyruvate into Acetyl CoA

The pyruvate dehydrogenase complex facilitates oxidative decarboxylation, the chemical reaction between glycolysis and the citric acid cycle.

Presentation
PDHA causes Lactic acidosis; large amounts of lactic acid in the blood but with a normal pyruvate/lactate ratio. Symptoms are varied, and include developmental defects (especially of the brain and nervous system), muscular spasticity and early death.

Genetics
PDHA is most commonly linked to the alpha unit of E1, but recessive variants exist.

Treatment
Use of a ketogenic diet has been described.

Current research is being conducted on the viability of Dichloroacetic acid to treat the lactic acidosis commonly accompanied by this disorder. Additionally, there is research being conducted on the viability of gene therapy for sufferers of this condition as well as many other mitochondrial defects.