Congenital disorders of glycosylation

Abstract

Congenital disorders of glycosylation (CDG) is a genetically heterogeneous and clinically polymorphic group of diseases caused by defects in various enzymes, the synthesis and processing of N-linked glycans or oligosaccharides into glycoproteins. Approximately half of all proteins expressed in cells are glycosylated to achieve their full functionality. Basically there are 2 variants of glycosylation: N-glycosylation and O-glycosylation. N-glycans are bound to the amide group of aspartine, whereas O-glycans are bonded to the hydroxyl group of serine or threonine. Synthesis of N-glycans occurs in 3 stages: the formation of nucleotide-linked sugars, assembly (in the cytosol and endoplasmic reticulum) and treatment (in the Golgi apparatus). Synthesis of O-glycans occurs mainly in the Golgi apparatus. The most frequently identified types of CDG are associated with a defect in the N-glycosylation pathway. CDGs are typically multisystem disorders with varying clinical manifestations such as hepatomegaly, cholestasis, liver failure, developmental delay, hypotonia, convulsions, facial dysmorphism and gastrointestinal disorders. Also histological findings showed liver fibrosis, malformation of the ducts, cirrhosis, and steatosis. CDGs typically present in the first months of life, and about 20% of patients do not survive to 5 years. The first line of CDG screening is based on the analysis of N-glycosylation of transf ferin. Exome sequencing or targeted gene panel is used for diagnosis. Several CDG subtypes are amenable to teraphy with mannose and galactose.