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. Author manuscript; available in PMC: 2023 Jun 1.
Published in final edited form as: Trends Mol Med. 2022 May 10;28(6):463–481. doi: 10.1016/j.molmed.2022.04.003

Fig 1: Therapy options for MPI-CDG, PGM1-CDG and PMM2-CDG.

Fig 1:

In MPI-CDG, the impaired conversion of fructose-6-P to mannose-6-P due to the defect of the mannose-6-phosphate-isomerase can be addressed therapeutically by supplementation of mannose, which provides additional substrate after the biochemical block.

In PMM2-CDG, the conversion of mannose-6-phosphate to mannose-1-phosphate is impaired due to a defect of phosphomannomutase-2, resulting in decreased availability of GDP-mannose, which is used for glycosylation reactions in the endoplasmatic reticulum. Intravenous supplementation of lipophilic mannose-1-P, using liposomes as a carrier, could potentially bypass the metabolic block in PMM2-CDG and hereby, directly correct the glycosylation cascade in the cells. This approach is currently being investigated and might be a therapy option for PMM2-CDG in the future.

In PGM1-CDG, defective phosphoglucomutase-1 leads to impaired interconversion of glucose-1-phosphae and glucose-6-phosphate. Supplementation of oral D-galactose bypasses the metabolic block and hereby, directly increases the availability of substrate for glycosylation.

As a result of these therapeutical approaches, glycosylation of common proteins (for example, transferrin) is restored.