Unexpected genetically determined immune dysregulation with liver involvement: GIMAP5 therapeutic dilemmas between targeted therapy and HSCT.

Introduction: Biallelic loss-of-function mutations in the GTPase of immunity-associated protein 5 ( Methods: We utilized trio-based clinical exome sequencing, flow cytometric immunophenotyping, protein expression profiling, and curated database analysis to evaluate the clinical trajectories. Results: The 11-year-old proband presented with autoimmune cytopenias, severe viral infections, and early biochemical liver anomalies. Genetic analysis identified compound heterozygous variants (p.Leu204Pro and p.Arg214Ter) in Discussion: This observation suggests complex genotype-phenotype interactions, raising the question of whether partial GIMAP5 deficiency might subtly predispose to localized vascular anomalies under specific environmental or epigenetic conditions, likely requiring multi-hit mechanisms. Therapeutically, the proband achieved sustained clinical remission of cytopenias through immunomodulation with the mTOR inhibitor sirolimus. These findings expand the phenotypic spectrum of this disorder, underscoring a dual role in immune and endothelial homeostasis. Furthermore, the successful application of sirolimus highlights the efficacy of precision medical management as a viable strategy to stabilize patients, allowing time to carefully weigh the risks and benefits of definitive interventions, such as hematopoietic stem cell transplantation.