Glycosylation Disorders with Immunodeficiency

Glycosylation refers to the attachment of sugars to proteins, a normal process required for the healthy function of cells. Glycosylation can impact how cells communicate, respond to their environment, grow and function. Because glycosylation regulates a wide range of activities in cells throughout the body, defects in glycosylation can cause extensive and severe symptoms. In some cases, these impairments disrupt the immune system, resulting in immunodeficiency. In some cases, these impairments disrupt the immune system, resulting in immunodeficiency.

NIAID scientists research genetic causes for glycosylation disorders with immunodeficiency, a set of rare diseases, and investigate the role that glycosylation plays in bacterial and viral infections. This research benefits people affected by these disorders and increases scientific knowledge of pathogens.

Researchers have not yet identified the cause of many forms of glycosylation disorders with immunodeficiency. However, in 2014, NIH scientists discovered a disorder caused by mutations in the PGM3 gene, resulting in defective sugar metabolism that leads to problems with glycosylation, especially in immune cells.

People with PGM3 gene mutations may experience the following symptoms:

  • Susceptibility to bacterial and viral infections
  • Allergies, including food allergy
  • Asthma
  • Eczema
  • Autoimmunity
  • Developmental delays, including motor and cognitive impairments

If a clinician suspects a patient may have a glycosylation defect, they may analyze protein samples to measure sugars and look for deficiencies or abnormalities.

People who have glycosylation disorders with immunodeficiency 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.

Interestingly, glycosylation defects also may protect people against microbes that rely on glycosylation for growth and infection. In 2014, NIH researchers identified two cases in which defective glycosylation protected people against specific viral infections. Based on insights gleaned from the study of glycosylation disorders, investigators at NIH are also exploring the use of glycosylation inhibitors to prevent and control viral infections.

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