Irena Muffels

Abstract Mitochondrial diseases frequently affect the brain leading to severe and disabling neurological symptoms. The heteroplasmic m.3243 A > G mutation in MT-TL1, encoding mt-tRNALeu, is responsible for ~80% of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), which is one of the most characteristic mitochondrial syndromes, leading to disability and early death.

Abstract Background: Congenital Disorders of Glycosylation (CDG) are a rapidly expanding group of inherited metabolic diseases caused by defects in glycosylation. Although over 190 genetic defects have been identified, effective treatments remain available for only a few. We hypothesized that integrative analysis of multi-omics datasets from individuals with various CDG could uncover common molecular signatures and highlight shared therapeutic targets.

Abstract Background Phosphoglucomutase-1 (PGM1) plays a pivotal role in glycolysis, glycogen metabolism, and glycosylation. Pathogenic variants in PGM1 cause PGM1-congenital disorder of glycosylation (PGM1-CDG), a multisystem disorder with cardiac involvement. While glycosylation abnormalities in PGM1-CDG are treatable with galactose, cardiomyopathy does not improve suggesting a glycosylation-independent pathomechanism.