DESORDENES CONGÉNITOS DE LA GLICOSILACIÓN

ASTEGGIANO CARLA G

Villa General Belgrano

Conferencia; GlycoAr; 2016

Insituto Leloir (Buenos Aires)

Correct glycan synthesis is essential for developmental and physiological processes. The disruption of glycan synthesis results in a multisystem disease with usually a severe neurological involvement. Congenital Disorders of Glycosylation (CDG) are a rapidly growing group of autosomic recessive diseases (with exception of autosomal dominant EXT1/EXT2-CDG and X-linked MAGT1-CDG) that involve defects in the synthesis or remodeling of N- and O-glycoproteins as well as defects in glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation. Since the initial description of CDG in 1984, the molecular and clinical characterization of more than 110 CDG diseases due to different affected genes has contributed to the understanding of the physiologic role of cell glycosylation. The analysis of serum transferrin has been widely used as a screening test. The most frequent CDG type is called PMM2-CDG and it is due to altered N-glycosylation pathway caused by mutations in PMM2 gene. The genetic defect causes the enzymatic phosphomannomutase deficiency (PMM; EC 5.4.2.28) in PMM2-CDG patients. PMM2 is an enzyme that catalyzes the conversion of mannose-6-phosphate to mannose-1-phosphate, required for the synthesis of activated mannose substrate donors in the synthesis of the lipid-linked oligosaccharides (LLO) in ER. Reports indicated that CDG should be suspected in each patient with unexplained congenital syndrome with psychomotor impairment.