Novel ALG8 mutations expand the clinical spectrum of congenital disorder of glycosylation type Ih.

Congenital disorders of glycosylation (CDG) are an expanding group of inherited disorders caused by defects in the N- or O-Glycosylation of proteins and lipids. Several CDG subtypes have been described so far, including CDG type Ih which is caused by a deficiency of the dolichyl-P-Glc:Glc(1)Man(9)GlcNAc(2)-PP-dolichyl alpha1,3-glucosyltransferase (hALG8). The defect leads to an accumulation of Dol-PP-GlcNAc(2)Man(9) and Dol-PP-GlcNAc(2)Man(9)Glc(1) in the endoplasmic reticulum of patients' fibroblasts that can be detected by analyzing the lipid-linked oligosaccharyl intermediates.

A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy.

The following study describes the discovery of a new inherited metabolic disorder, dolichol kinase (DK1) deficiency. DK1 is responsible for the final step of the de novo biosynthesis of dolichol phosphate. Dolichol phosphate is involved in several glycosylation reactions, such as N-glycosylation, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, and C- and O-mannosylation.