Dolichol phospho-mannose

Interestingly, phenotypes of type Ib and Ic are reported to be milder than type la CDGS [14], Especially, the phenotype of PMI mutation (type Ib) does not show neurological symptoms. Because PMI mutation in CDGS type Ib does not inhibit dolichol-phospho-mannose synthesis from mannose, oral administration of mannose has been shown to be effective in type Ib [15]. 

Biosynthesis of GPI anchors starts with the core structure assembly by sequential addition of UDP-GlcNAc (followed by iV-deacetylation), dolichol-phosphate-mannose, and phospho-ethanolamine to phosphatidylinositol and culminates in the en bloc transfer to protein shortly after the protein is synthesized. However, the biosynthetic pathways can differ strikingly between different organisms with respect to specific modifications and fatty acid remodeling occurring after completion of the core glycan. This also applies for the point when certain modifications are introduced, e. g. before or after the transfer of the GPI-moiety to the protein. GPI anchors can be cleaved at defined positions by an array of enzymatic and chemical methods, respectively (O Fig. 5). Thus, it becomes possible to identify GPI-anchored proteins and, moreover, analyze the structure and biosynthesis of GPI anchors [103]. 

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