Pyruvate dehydrogenase deficiency

Pyruvate Dehydrogenase Deficiency (PDH) is a human genetic disease.

Inheritance and pathophysiology
It most commonly follows an X-linked inheritance pattern, but is approximately equally prevalent in both males and females. This is because heterozygote females commonly manifest severe symptoms, an unusual situation in X-linked conditions. Due to the genes involved being essential to life, some of the genetic causes are extremely rare, in the order of 1 in millions. 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.

Deficiencies of the regulatory complex (pyruvate dehydrogenase phosphatase) have also been investigated.

Presentation
PDH 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
PDH deficiency is most commonly linked to the alpha unit of E1, which is X-linked, but autosomal recessive variants also 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.