Defective Glycosyltransferases are Not Good for Your Health

The history of biochemical research on the structure and function of glycoproteins and glycolipids (glycoconjugates) dates back to the early 19th century (Montreuil, 1995). The variety of these macromolecules, their wide-spread distribution among all forms of life and their quantitative contribution to the bio-mass rank with those of proteins and nucleic acids. Nevertheless for a long period of time the lack of decisive information on the functions of glycoconjugates (Varki, 1993) discouraged most biochemists from entering this field. A series of discoveries over the past 25–30 years has slowly changed this attitude, e.g., the demonstration of mammalian lectins and of the association of defects in glycoconjugate metabolism with human diseases such as cancer, inflammatory and infectious diseases and various congenital diseases (Montreuil et al., 1996). Five autosomal recessive diseases have been reported to date (Table 1) in which a defect in the synthesis of asparagine-linked carbohydrate (N-glycans) has been clearly demonstrated. This presentation will focus on three of these diseases, carbohydrate-deficient glycoprotein syndromes Types I and II (CDGS I and II) and hereditary erythroblastic multinuclearity with a positive acidified serum lysis test (HEMPAS, Congenital Dyserythropoietic Anemia Type II). The study of these diseases should provide valuable information on the roles of N-glycans in human development.