Hypomorphic RAG deficiency: impact of disease burden on survival and thymic recovery argues for early diagnosis and HSCT

Schuetz, C.; Gerke, J.; Ege, M.; Walter, J.; Kusters, M.; Worth, A.; ... ; Primary Immune Deficiency Treat (2023)

Article / Letter to editor

Patients with hypomorphic mutations in the RAG1 or RAG2 gene present with either Omenn syndrome or atypical combined immunodeficiency with a wide phenotypic range. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but data are scarce. We report on a worldwide cohort of 60 patients with hypomorphic RAG variants who underwent HSCT, 78% of whom experienced infections (29% active at HSCT), 72% had autoimmunity, and 18% had granulomas pretransplant. These complications are frequently associated with organ damage. Eight individuals (13%) were diagnosed by newborn screening or family history. HSCT was performed at a median of 3.4 years (range 0.3-42.9 years) from matched unrelated donors, matched sibling or matched family donors, or mismatched donors in 48%, 22%, and

• Infections
• autoimmunity
• damage prior HSCT
• In patients with

• All authors: Schuetz, C.; Gerke, J.; Ege, M.; Walter, J.; Kusters, M.; Worth, A.; Kanakry, J.A.; Dimitrova, D.; Wolska-Kusnierz, B.; Chen, K.; Unal, E.; Karakukcu, M.; Pashchenko, O.; Leiding, J.; Kawai, T.; Amrolia, P.J.; Berghuis, D.; Buechner, J.; Buchbinder, D.; Cowan, M.J.; Gennery, A.R.; Güngör, T.; Heimall, J.; Miano, M.; Meyts, I.; Morris, E.C.; Rivière, J.; Sharapova, S.O.; Shaw, P.J.; Slatter, M.; Honig, M.; Veys, P.; Fischer, A.; Cavazzana, M.; Moshous, D.; Schulz, A.; Albert, M.H.; Puck, J.M.; Lankester, A.C.; Notarangelo, L.D.; Neven, B.; European Soc Immunodeficiencies; Inborn Errors Working Party IEWP; European Soc Blood Marrow Trans; Primary Immune Deficiency Treat
• Date: 2023-02-16
• Journal: Blood
• Volume: 141
• Issue: 7
• Pages: 713 - 724
• DOI: doi:10.1182/blood.2022017667
• Link: https://ashpublications.org/blood/article/141/7/713/486874/Hypomorphic-R...