We report here that, by using tracer-based metabolomics, we found that galactose treatment of PGM1-CDG fibroblasts metabolically re-wires their sugar metabolism, and as such replenishes the depleted levels of galactose-1-P, as well as the levels of UDP-glucose and UDP-galactose, the nucleotide sugars that are required for ER- and GA-linked glycosylation, respectively.
This variant has been linked to a congenital disorder of glycosylation (PGM1-CDG), explaining the clinical picture of short stature, cleft palate, liver engagement and cardiomyopathy.
The early molecular genetic analysis and multisystem assessment were here found to be essential to the diagnosis of PGM1-CDG and the provision of timely and proper treatment.
Only for few CDG, potentially curative therapies are being used, including dietary supplementation (e.g., galactose for PGM1-CDG, fucose for SLC35C1-CDG, Mn<sup>2+</sup> for TMEM165-CDG or mannose for MPI-CDG) and organ transplantation (e.g., liver for MPI-CDG and heart for DOLK-CDG).
Recently, with the successful use of d-galactose in Phosphoglucomutase 1 (PGM1)-CDG, other CDG types have been trialed on galactose and with an increasing number of potential nutritional therapies.