A functional study helps describe a new severe metabolic syndrome caused by Coenzyme A deficiency
The Journal Inherited Metabolic Disease has published a study from the Spanish Network Research Centre for Rare Diseases (CIBERER) describing a new inborn error of metabolism generated by a failure in the synthesis of Coenzyme A (CoA). CoA is an essential molecule in many energy-producing metabolic processes in our cells. Four enzymes are involved in the synthesis of CoA, and this is the first time that diseases associated with defects in PPCDC (phosphopantothenoylcysteine decarboxylase) have been described.
Researchers described the metabolic defect in two sisters who died from severe heart problems. The first baby died ten days after she was born, and the second at four months old. DNA was extracted from the girls to look for possible mutations, and scientists detected two variants of uncertain clinical significance (i.e., mutated copies of the gene not known yet to have negative health implications) of the PPCDC gene. Subsequently, they performed studies to analyse whether the structure of the PPCDC protein produced by these variants was affected in any way, and they found that it was more unstable. Next, the concentration of CoA in the patients' cells was measured, and they saw CoA levels were 50% below standard: these cells had an evident energetic impairment and showed mitochondria dysfunctions. The final study aimed at verifying that the variants found produced the same effects in yeast cells, and the results of the experiments supported this fact.
The description of this new congenital metabolic defect opens the door to early detection, which could make available supplementation therapy to address PPCDC enzyme deficiency.