Introduction Hematopoietic stem cell transplantation (HSCT) is a curative treatment for pediatric hematologic and immunologic disorders, with successful immune reconstitution being critical for long-term survival. We report the unique case of persistent hypogammaglobulinemia following fully matched HSCT from a phenotypically normal sibling donor carrying a heterozygous RAG1 gene mutation. Methods A 13-year-old girl with EBV-associated NK/T-cell lymphoproliferative disorder underwent fully matched sibling HSCT from her mutation-carrying donor. Whole-exome sequencing confirmed the RAG1 c.994CT (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 This case demonstrates that heterozygous variants in genes critical for hematopoietic reconstitution (such as RAG1 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.
Wu et al. (Wed,) studied this question.