Case report: Persistent hypogammaglobulinemia following hematopoietic stem cell transplantation from a sibling donor with heterozygous RAG1 mutation

Introduction: gene mutation. Methods: c.994C>T (p.Arg332*) mutation in both donor and recipient. Post-transplant monitoring included serial lymphocyte subset measurements and immunoglobulin level monitoring over a 5-year period. Results: Despite successful engraftment and quantitative T- and B-cell recovery, the patient developed persistent hypogammaglobulinemia. Serum IgG levels declined to below 4g/L at 4 months post-HSCT and remained persistently below 2g/L from 11 months onwards (with only one measurement of 2.57g/L during this period). IgA levels remained consistently below 0.2g/L, becoming undetectable by 11 months and remaining so. IgM levels dropped below the detection threshold at 2 months and demonstrated only partial recovery by 18 months (peak: 0.29g/L). The patient experienced recurrent respiratory infections, necessitating long-term immunoglobulin replacement therapy. Conclusions: mutations) may still lead to significant immunodeficiency post-transplantation. Our findings strongly suggest that potential donors carrying such mutations require careful evaluation, with non-carrier donors being preferentially selected when available, especially in the context of HSCT.