Glycosylation Disorders With Immunodeficiency
Glycosylation refers to the attachment of sugars to proteins, a normal process required for the healthy function of cells. Defects in glycosylation can impair the growth or function of cells and tissues in the body, and in some cases, the immune system is disrupted, resulting in immunodeficiency.
Changes in glycosylation can alter the amount and virulence of viruses produced by human cells.
In 2014, researchers at the NIH discovered a new immunodeficiency caused by glycosylation defects. People with this disorder have mutations in the PGM3gene, resulting in defective sugar metabolism and subsequent problems with glycosylation, especially in immune cells. These findings suggest that glycosylation defects may be involved in more common immune disorders, like allergy or autoimmunity.
Signs and Symptoms
Glycosylation can impact how cells communicate, respond to their environment, grow, and function. Because it regulates a wide range of activities in cells found throughout the body, defects in glycosylation can cause extensive and severe symptoms.
People with PGM3 gene mutations may experience the following symptoms:
- Susceptibility to bacterial and viral infections
- Allergies, including food allergy
- Eczema, a skin disorder
- Developmental delays, including motor and cognitive impairments
Interestingly, glycosylation defects may protect people against microbes that rely on glycosylation for growth and infection. In 2014, NIH researchers identified two cases where defective glycosylation protected against specific viral infections.
Glycosylation disorders with immunodeficiency cover a range of symptoms and may not be limited to PGM3 gene mutations. If glycosylation defects are suspected, protein samples may be analyzed to measure sugars and look for deficiencies or abnormalities.
Treatment and Research
People with these disorders may receive therapies commonly used to treat infections, allergies, and skin problems. For people with PGM3 defects, NIH researchers are evaluating ways to boost the production of the missing sugars by supplementing with other types of sugar. Investigators at NIH are also exploring the use of glycosylation inhibitors to prevent and control viral infections.