Linker for activation of T cell (LAT) deficiency is a rare form of severe combined immunodeficiency (SCID), characterized by a disruption in T cell receptor (TCR) signaling, leading to compromised immune responses and immune dysregulation.
We report a 5-year-old Saudi boy, who presented at age 4 months with diarrhea, disseminated Bcgitis, and AIHA. Genetic analysis showed a novel biallelic deletion of the exons 9-11 in LAT gene (c.846-1054cnv), predicted to result in a nonfunctional protein that matches his clinical phenotype. He was also found to have homozygous UNC80 (c.2213G>A) gene mutation, which is related to neurodegenerative disease. He underwent unconditioned FMD HSCT.
Our patient underwent unconditioned MSD HSCT to avoid chemotherapy-induced neurotoxicity. STR showed 100% donor lymphoid engraftment at days +30, +90, and +120. He developed acute grade 1/2 GVHD (skin and liver), which resolved with immunosuppression. Currently, he maintains a good quality of life on IVIG, Pentamidine, and Prednisolone. While conditioned HSCT is preferred for long-term immune reconstitution in LAT-related SCID, the associated neurodegenerative disease and risk of BCG reactivation may warrant future consideration of a second HSCT. Literature suggests fully matched transplants improve survival, though long-term outcomes remain unclear due to limited patient data.
Unconditioned MSD HSCT can achieve full donor lymphoid engraftment in LAT-related SCID while minimizing chemotherapy-associated neurotoxicity, though long-term immune reconstitution may require further intervention. More data are needed to assess long-term outcomes, especially in patients with comorbidities and GVHD risk.
