RAG2 is an essential gene, encoding enzymes involved in recombination of genes for Immunoglobulin and T-cell receptor proteins. Several mutations have been described, with a variety of clinical phenotypes ranging from severe combined immunodeficiency (SCID) to autoimmunity.
For most-severe manifestations, Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT) is the standard treatment. This carries significant risk of mortality. Better outcomes are expected if performed in infancy. Delay resulting in advanced disease may preclude this being an option.
Gene therapy is rapidly advancing with opportunity to develop new ways of approaching treatment options.
We review a patient case and consider feasibility of genetic screening in patients with CVID and evaluate outcomes of Bone marrow transplantstion in similar cases.
Patient case review: 40-year-old female, presenting aged 25 with Myasthenia gravis and incidental discovery of B and T cell lymphopenia, alongside recurrent infections. Aged 29 she developed autoimmune macrophagic myofascitis. Aged 39 she was enrolled onto the BRIDGE study with identification of a likely pathogenic novel RAG2 gene mutation. We review the timeline of events. We discuss evaluation for Bone marrow transplant and available literature for outcomes in similar cases.
Early genetic screening may be helpful in selecting appropriate patients with immunodeficiency for bone marrow transplantation, but more data is needed.
This case highlights the challenges associated with decision making when approaching treatment options in patients, where literature for genetically and phenotypically similar, but not identical patients, is available.