Beneficial effects of Glc-1,6-P2 modulation on mutant phosphomannomutase-2

The metabolite Glucose-1,6-bisphosphate (Glc-1,6-P₂) plays a vital role in human metabolism, and is a crucial activator and stabilizer for phosphomannomutase-2 (PMM2) – mutations within this protein propagate the most common congenital disorder of glycosylation (PMM2-CDG). In vivo, Glc-1,6-P₂ is hydrolysed by phosphomannomutase-1 (PMM1), predominantly in the brain, under the influence of inosine monophosphate (IMP). In the present study, we employed knock-out PMM1 in ^{Arg141His/Phe119Leu}PMM2 patient-derived fibroblasts and investigated the phenotypic improvement.