RAG2-related disorders are a set of conditions causing severe combined immunodeficiency (SCID), a problem in the immune system. This means people with this condition have a weak or no response to infections.
Specifically, those with SCID due to RAG2-related disorders lack T-cells and B-cells, essential for a proper immune system. This makes their immune system weak, and they struggle to fight infections, often getting severe and recurring infections from infancy. If not treated, these infections might lead to death in the first year of life. Infants with this condition may also experience slow growth and ongoing diarrhea. Omenn syndrome is a special kind of immune deficiency that can happen in some with RAG2-related disorders. Unlike regular RAG2-related SCID, those with Omenn syndrome have detectable T-cells, but these cells don’t work well. This leads to severe, repeat infections along with skin issues, hair loss, swollen lymph nodes, ongoing diarrhea, and a larger liver and spleen.
Treatment usually involves a stem cell transplant, where blood cell-forming cells are replaced. Most often, this comes from bone marrow, but sometimes it’s from cord blood. While this treatment can be effective, some might still need immunoglobulin therapy (antibody infusions) afterward. However, there can be serious complications from the transplant. The best chance of survival is when the transplant comes from a matched sibling and is done soon after birth.
This group of conditions is caused by pathogenic (disease-causing) variants in the RAG2 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Ashkenazi Jewish descent have a 1 in 821 chance to be a carrier.
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Revised November 2023
