Master Pyruvate Dehydrogenase Deficiency with Picmonic for Medicine

Pyruvate Dehydrogenase Deficiency is typically inherited in an X-linked manner due to mutations in the PDHA1 gene, where males are more frequently affected, and females may be carriers or show milder symptoms.

Because this enzyme complex requires thiamine as a cofactor, a pyruvate dehydrogenase deficiency can also be acquired from a thiamine deficiency.

The pyruvate dehydrogenase enzyme complex consists of three enzymes that transform pyruvate to acetyl CoA via pyruvate decarboxylation. Deficiency of this enzyme causes a backup of pyruvate, which is commonly converted to alanine.

Individuals can present with severe neurologic defects due to a large energy deficit. Severe enzyme deficiencies can also lead to congenital brain malformation due to lack of ATP during neural development.

Because acetyl CoA cannot be produced to enter the Kreb cycle, aerobic metabolism is severely impaired and the body uses anaerobic pathways to produce ATP. This causes a severe elevation of lactic acid.

Treatment includes thiamine supplementation and ketogenic diets including amino acids like lysine and leucine to limit lactic acidosis.

Lysine and leucine are the only purely ketogenic amino acids, which are used in the treatment of individuals with pyruvate dehydrogenase deficiency to limit lactic acidosis.