Pyruvate Dehydrogenase Deficiency

Pyruvate Dehydrogenase Deficiency

Pyruvate dehydrogenase is a complex of enzymes that facilitates the conversion of the food we eat into the energy our cells need to function. Deficiency in this enzyme complex leads to the accumulation of the protein pyruvate and its conversion into lactic acid or a decrease in energy production, with damage mainly affecting the brain, which requires a significant amount of energy to function and grow.

It is an inherited disease caused by mutations in one of the genes (PDHA1, PDHB, DLAT, PDHX, PDP1) that, through the production of the pyruvate dehydrogenase complex, enable the transformation of pyruvate protein into acetyl-CoA, as the first step in a process that leads to energy production for our cells. The disease can be transmitted by inheriting the mutated gene from one’s mother (X-linked recessive transmission) in the case of the PDHA1 gene, or in cases where both parents are carriers of the mutation (autosomal recessive transmission) for genes PDHB, DLAT, PDHX, PDP1.

The severity of symptoms can vary greatly from individual to individual. In severe cases, the child may present with below-normal weight at birth, structural brain lesions (more often in girls), and characteristic somatic appearance. In other cases, symptoms may occur after the child’s birth, with an inability to feed, lethargy, and increased respiratory rate (tachypnea). These symptoms are often associated with the accumulation of ammonia and lactic acid in the body.