PMM2-CDG (also known as CDG-1a) is short for phosphomannomutase 2-congenital disorder of glycosylation and is the most prevalent congenital disease of glycosylation (CDG). Glycosylation is the process of adding sugar chains, also called glycans, to the surface of proteins. More than 50% of proteins in the body are glycosylated and this process is critically important to ensure the correct structure and function of proteins.
Proteins are complex molecules that do most of the work in cells, and thus their proper function drives health and disease. Glycans play an important role in protein folding and stability and protein-protein interactions. Glycans also participate in cell signaling and many intracellular processes, including immune system regulation and virus recognition and cell adhesion and trafficking.
PMM2-CDG is caused by genetic mutation in phosphomannomutase 2 (PMM2), which results in the protein having reduced activity. PMM2 is an enzyme that converts mannose-6-phosphate to mannose-1-phosphate, which is required to insert the mannose sugar building block into developing glycans that are crucially important for proper protein structure and function. The deficiency of mannose-1-phosphate therefore disrupts the process of N-glycosylation and causes a wide array of symptoms and, in many cases, can be life-threatening. Mortality from PMM2-CDG is estimated to be as high as 20% over the first five years of life.
While there are currently no FDA or EMA approved therapies to treat the underlying cause of PMM2-CDG, Glycomine hopes to change that. Glycomine is developing GLM101, a mannose-1-phosphate (M1P) replacement therapy designed to deliver mannose-1-phosphate directly into cells and thereby bypass the PMM2 enzyme deficiency.
Diagnosing PMM2-CDG can be a long and difficult journey. If a doctor suspects PMM2-CDG, they may do a variety of tests, including a blood test to measure transferrin. Because genetic testing is the most accurate type of test, it may help reduce the amount of time it takes for a patient to get diagnosed.
If you suspect you have PMM2-CDG, your health care professional may order a no cost genetic test by completing the attached form and sending it to . The form may also be faxed to (715) 406-4175. If you have additional questions regarding no cost genetic testing for PMM2-CDG, please contact us at .