Congenital disorders of glycosylation (CDG) comprise a group of
inborn errors of metabolism with abnormal glycosylation of
proteins and
lipids. Patients with defective
protein N-glycosylation are identified in routine metabolic screening via analysis of serum
transferrin glycosylation. Defects in the assembly of the
dolichol linked Glc(3)
Man(9)GlcNAc(2)
glycan and its transfer to
proteins lead to the (partial) absence of complete
glycans on
proteins. These defects are called CDG-I and are located in the endoplasmic reticulum (ER) or cytoplasm. Defects in the subsequent processing of
protein bound
glycans result in the presence of truncated
glycans on
proteins. These defects are called
CDG-II and the
enzymes involved are located mainly in the Golgi apparatus. In recent years, human defects have been identified in
dolichol biosynthesis genes within the group of CDG-I patients. This has increased interest in
dolichol metabolism, has resulted in specific recognizable clinical symptoms in CDG-I and has offered new mechanistic insights in
dolichol biosynthesis. We here review its biosynthetic pathways, the clinical and biochemical phenotypes in
dolichol-related CDG defects, up to the formation of dolichyl-P-
mannose (Dol-P-Man), and discuss existing evidence of regulatory networks in
dolichol metabolism to provide an outlook on therapeutic strategies.