GMPPB-CDG Results in Lysosomal Dysfunction and Acid Alpha-Glucosidase Deficiency.

ABSTRACT: GDP-mannose pyrophosphorylase B (GMPPB) deficiency is a congenital disorder of glycosylation due to pathogenic variants of the GMPPB gene. GMPPB catalyzes GDP-mannose synthesis, an early step in multiple glycosylation pathways, including N-glycosylation, O-mannosylation, C-mannosylation, and glycosylphosphatidylinositol-anchor formation. In fibroblasts (N = 3), myoblasts (N = 4) and in muscle biopsies (N = 4) from a total of 7 GMPPB-deficient patients we found evidence of glycogen accumulation, both in cytosol and in lysosome-like vesicles, presence of heterogeneous storage material, and expansion of the lysosomal compartment. Due to the excess of glycogen in cells and tissues, we investigated acid alpha-glucosidase (GAA) in cultured GMPPB fibroblasts. GAA activity was reduced in GMPPB cel

SUBMITTER: Damiano C 

PROVIDER: S-EPMC12815487 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature