PLCG1 gene mutation in a child with autoimmune hemolytic anemia: a case report

Autoimmune hemolytic anemia (AIHA) is a highly heterogeneous disease characterized by immune-mediated destruction of red blood cells through cellular and humoral mechanisms, complement activation, cytokine release, and bone marrow compensation. Clinically, AIHA exhibits a broad spectrum of severity, ranging from mild or compensated anemia to life-threatening anemia. Traditionally, therapeutic approaches have relied on corticosteroids, immunosuppressive agents, and splenectomy as the mainstay treatment. Increasing evidence suggests that genetic factors, including variants in the PLCG1 gene—which plays a critical role in immune signaling and regulation—may contribute to disease pathogenesis. Herein, we report a case of a 13-year-old boy diagnosed with AIHA at 11 months of age. The patient initially presented with pallor and jaundice associated with a febrile illness. The diagnostic workup revealed anemia, reticulocytosis, a peripheral blood smear consistent with AIHA, low serum-free haptoglobin levels, and a positive direct Coombs test result. Next-generation sequencing identified a novel heterozygous PLCG1 missense variant, c.2617C > T p.(Arg873Trp), which has not been previously reported. This case expands the spectrum of PLCG1 -associated immune dysregulation and suggests that this variant may contribute to the development of AIHA. This report provides a rationale for functional studies on the role of PLCG1 in human disease and immune dysregulation.