Hope for patients with Methylmalonic aciduria

This is the first time that MMA has been studied using a multi-omics approach (genomics, transcriptomics, proteomics, metabolomics).

By opting to expand significantly their molecular investigation, the researchers considered not only the disease’s genetic cause but also its consequences in terms of RNA, proteins, and protein function. This enabled the consortium, as part of this study, to develop a diagnostic strategy that correctly diagnosed 84 percent of the patients examined.

The multi-omics data also showed that MMA patients use an alternative energy source to help deal with the fact that a vital enzyme is defective. However, in patients, this alternative energy source usually is not able to sufficiently compensate for energy production lost. In in vitro experiments with patient cells, the researchers succeeded in boosting energy production to near-normal levels by supplying such an alternative energy source.

Reference:

Bernd Wollscheid et al,Integrated multi-omics reveals anaplerotic rewiring in methylmalonyl-CoA mutase deficiency,Nature Metabolism,doi 10.1038/s42255-022-00720-8