Abstract: Objective We aimed to report the clinical manifestations, immunological features, genetic diagnosis and treatments of two cases with LRBA (LPS-responsive beige-like anchor protein) gene mutation. Methods Two male cases with LRBA gene mutations were enrolled in our study. The clinical features, immunological features and treatments of the two patients were retrospectively summarized. The lymphocyte subsets were detected by Flow Cytometry. WES was adapted for genetic analysis and the LRBA gene mutations were confirmed by Sanger sequencing，while the deletion of a gene was confirmed by fluorescence quantitative PCR. Results Patient 1 (P1) presented with recurrent throbocytopenia and hematocytopenia for six years. He also had recurrent fungal infection, persistent EBV viraemia, growth retardation and apparent hepatosplenomegaly. Patient 2 (P2) presented with recurrent thrombocytopenia after birth. They were diagnosed at the age of 13 years and 4 months respectively. Both of them presented with increased naive B cells and decreased memory B cells. P1 presented with decreased levels of immunoglobulin(Ig) M, IgG and IgA. Decreased naive CD4+ T and CD8+ T cells, expanded central memory CD4+ T and CD8+ T cells, reduced CD4+ T lymphocytes, B lymphocytes and NK cells, and increased CD8+ T cells were also observed in P1. P2 presented with increased IgG level. Sequencing results revealed that P1 had c.1933C>T (p.R645X) mutation and exon 29 deletion in LRBA gene. P2 had compound heterozygous mutations in LRBA gene (c.3778G>C, p.A1260P and c.1570G>A, p.G524S). Finally, P2 underwent hematopoietic stem cell transplantation (HSCT) and was currently in remission. Meanwhile P1 was under symptomatic treatment. Conclusion LRBA deficiency has a wide spectrum of phenotypes, characterized by hypogammaglobulinemia, recurrent infections, autoimmune diseases and susceptibility to EBV infection. Intravenous immune globulin could help relieve infection. Abatacept targeted therapy and HSCT might be the availabe therapeutic options for patients with LRBA deficiency.