Diagnostic and Therapeutic Approaches in Congenital Disorders of Glycosylation.

Abstract

Congenital disorders of glycosylation (CDG) constitute an increasing group of inborn metabolic disorders, with more than 170 described diseases to date. A disturbed glycosylation process characterizes them, with molecular defects localized in distinct cell compartments. In CDG, N-glycosylation, O-glycosylation, glycosylation of lipids (including phosphatidylinositol) as well as the glycosaminoglycan synthesis can be affected. Owing to the importance of glycosylation for the function of concerned proteins and lipids, glycosylation defects have diverse clinical consequences. CDG affected individuals often present with a non-specific multivisceral syndrome including neurological involvement, intellectual disability, dysmorphia, and hepatopathy. As CDG are rare diseases frequently lacking distinctive symptoms, biochemical and genetic testing bear important and complementary diagnostic roles.After an introduction on glycosylation and CDG, we review current biomarkers and analytical techniques in the field. Furthermore, we illustrate their interests in the follow-up of proven therapeutic approaches including D-mannose in MPI-CDG, D-galactose in PGM1-CDG, and manganese (MnSO₄) in TMEM165-CDG.