Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections

Genetic defects in MOGS, the gene encoding mannosyl-oligosaccharide glucosidase(the first enzyme in the processing pathway of N-linked oligosaccharide), cause the rare congenital disorderof glycosylationtype IIb (CDG-IIb), also known as MOGS-CDG. MOGS is expressed in the endoplasmic reticulum and is involved in the trimming of N-glycans. We evaluated two siblings with CDG-IIb who presented with multiple neurologic complications and a paradoxical immunologic phenotype characterized by severe hypogammaglobulinemiabut limited clinical evidence of an infectious diathesis. A shortened immunoglobulin half-life was determined to be the mechanism underlying the hypogammaglobulinemia. Impaired viral replicationand cellular entry may explain a decreased susceptibility to infections.