MOGS-CDG is autosomal recessive disorder, caused by biallelic pathogenic variants in MOGSgene, which codes for mannosyl-oligosaccharide glucosidase. MOGS enzyme is involved in the first step of N-glycosylation in the ER, where terminal glucose residues are removed from the newly synthed N-linked glycans. MOGS deficiency, therefore, leads to accumulation of glucose-capped high-mannose glycans, which affects the protein structure and function.
While a big group of CDG can be diagnosed by CDT or glycomics methods, these are normal in most MOGScases. Some MOGS-CDG patients have an abnormal CDT profile consistent with CDG type II. However, some MOGS-CDG patients do not show abnormal transferrin pattern and can often be missed by serum glycan based screening.
In addition to abnormal glycosylation, MOGS-CDG patients have increased excretion of Glc3Man which is pathognomonic. Glc3Man can be detected in urine by for example LC-MS/MS methods.
Finally, the diagnosis in the majority of the patients is usually made by genetic testing such as WES, although the interpretation of the results is vastly guided by biochemical (functional) tests.
MOGS