Congenital Disorders in Glycosylation

Abstract

Congenital disorders of glycosylation (CDG) is a fast growing group of autosomal recessive inherited diseases caused by defects in glycosylation. The biosynthesis of the glycans is a pathways which occurs in the endoplasmic reticulum and Golgi complex thanks to highly specific enzymes: glycosidases and glycosyltransferases. The sequential addition of monosaccharides needs precursors which are nucleotide sugars or dolichyl sugars. CDG are divided into two groups: CDG I composed of defects in enzymes involved in the assembly of dolicholpyrophosphate oligosaccharide and in the transfer of oligosaccharide from dolicholpyrophosphate to an Asn residue on nascent proteins; CDG II composed of defects in the processing of protein-bound glycans with alterations in enzymes or in the transporters of monosaccharides. Clinical symptoms are poorly specific and multisystemic, biochemistry provides the diagnosis: Isoelectrofocalisation and western blot of serum transferrin and some other glycoproteins; Measurement of enzyme activities; Research of gene mutations. Today, thirteen CDG are identified, the most frequent is CDG Ia due to a defect in the phosphomannomutase activities and CDG Ib due to a defective phosphomannose isomerase, is the only CDG which is successfully treated with mannose.