Chapter 94 - Congenital Disorders of Protein Glycosylation

Abstract

Congenital defects of glycosylation (CDG) are genetic diseases due to deficient glycosylation of glycoproteins and glycolipids. This chapter is devoted to protein glycosylation disorders. These can be divided into three groups: (1) defects in protein N-glycosylation (n: 16); (2) defects in protein O-glycosylation (n: 11); and (3) defects in combined protein N- and O-glycosylation (n: 19). CDG patients mostly show neurological disease associated with variable involvement of nearly all other organs. Only a few CDG are mono-organ diseases such as TUSC3-CDG (brain), EXT1/EXT2-CDG (cartilage), GNE-CDG (skeletal muscles), SEC23B-CDG (erythrocytes). Inheritance is autosomal recessive except for MAGT1-CDG (X-linked) and EXT1/EXT2-CDG (autosomal dominant). Two screening techniques are available: serum transferrin isofocusing (or similar techniques) for the diagnosis of protein N-glycosylation disorders associated with sialic acid deficiency, and serum apolipoprotein C-III isofocusing for the diagnosis of core 1 mucin type O-glycans. An efficient therapy is available for only one CDG namely MPI-CDG (oral mannose). There is no doubt that most CDG types remain undiagnosed since about 1% of the human genome is involved in glycosylation. Next-generation sequencing techniques will play an increasingly important role in the diagnosis of novel CDG. The novel CDG nomenclature is used that consists of the official gene symbol (unitalicized) followed by “-CDG.”