Other forms of congenital disorders of glycosylation

Psychomotor retardation; microcephaly; hypotonia; seizures.

In addition to the deficiency of phosphomannose mutase which characterises CDG-Ia (Chapter 104), several other steps in the formation of glycoproteins have been identified [1]. For N-linked glycosylation, glycan assembly takes place first on the cytoplasmic side of the endoplasmic reticulum (ER), and then on the lumenal aspect, resulting in the formation of the lipid-linked oligosaccharide dolichylpyrophosphate-GlcNAc2Man9Glc3 (Figure 105.1). The oligosaccharide side-chain is then transferred en bloc to selected asparagines of nascent proteins. Then the glycan of the newly formed glycoprotein is processed in the ER, where the three glucoses are removed, and then in the Golgi, where the mannose-rich core is removed and replaced, typically with two residues each of N-acetylglucosamine, galactose, and sialic acid (Figure 105.2).