Curative hematopoietic stem cell transplantation in a child with specific granule deficiency due to a homozygous SMARCD2 variant

• Published in: Pediatric hematology oncology journal 2024-12, Vol.9 (4), p.311-314
• Main Authors: Menon, Janaki, Raj, Revathi, Manakkad, Shiny Padinjarayil, Edavazhippurath, Athulya, Saravanan, Priya, Unnikrishnan, Anjit, Uppuluri, Ramya, Kandy, Sheena Othayoth, Saphia, Shammy, George, Kalpana, Dhanasooraj, Dhananjayan, Govindaraj, Geeta Madathil
• Format: Article
• Language: English
• Subjects: Hematopoietic stem cell transplantation; Phagocytic defect; Specific Granule Deficiency
• ISSN: 2468-1245; 2468-1245
• DOI: 10.1016/j.phoj.2024.11.103

Children with recurrent, severe infections that respond poorly to treatment are likely to have an underlying inborn error of immunity. A three-year-old male child of non-consanguineous parentage presented with recurrent severe infections from the neonatal period, including abscesses, pneumonia, diarrhea, meningitis, cystitis, and pyelonephritis. The child had subtle dysmorphic features. The dihydro rhodamine assay was abnormal, and the peripheral smear showed hypogranular, hypolobated neutrophils. Clinical exome sequencing revealed a homozygous variant in the SMARCD2 gene, confirming the diagnosis of specific granule deficiency 2. The child underwent a haploidentical hematopoietic transplant and is asymptomatic five months post-transplant. Conditioning chemotherapy included rabbit anti-thymocyte globulin/treosulphan/thiotepa/fludarabine. The CD34 dose infused was 15 x 106/kilogram recipient body weight. The infused product was TCR alpha/beta and CD19 depleted with preserved TCR gamma/delta cells. This case demonstrates that although ultra-rare inborn errors of immunity are often diagnosed by next-generation sequencing, simple hematological and immunological tests provide valuable clues. Timely hematopoietic stem cell transplantation is curative.