CVID-8 in a Compound Heterozygous LRBA Mutation Carrier Presenting as Refractory ITP in a Pediatric Patient

Background: Common Variable Immunodeficiency (CVID), a heterogeneous syndrome characterized by hypogammaglobulinemia and defective humoral immunity, is the most prevalent symptomatic primary immunodeficiency. CVID-8 is a monogenic variant due to bi-allelic mutation in the LRBA gene. Individuals carrying a single mutated LRBA allele are considered phenotypically healthy. However, immune dysregulation may arise in certain heterozygous carriers likely via haploinsufficiency or dominant-negative activity. LRBA critically regulates CTLA-4 recycling, directly linking this deficiency to immune checkpoint biology. Case Presentation: We report a 7-year-old female, born to consanguineous Lebanese parents, with a family history of thrombocytopenia, presented with chronic refractory ITP first diagnosed at age 2. The patient was resistant to multiple sequential therapeutic interventions including immunosuppressive agents and splenectomy. Whole exome sequencing (WES) detected compound heterozygous LRBA variants c.7937T>G (p.Ile2646Ser) and c.7046T>A p.Leu2349*, the former is pathogenic associated with CVID-8. Immunological assessment revealed hypogammaglobulinemia with suppressed IgG1, IgG3, IgA and IgM levels. Her latest hospitalization was marked by abdominal pain, impaired consciousness, acute liver injury, coagulopathy, peripheral leukocytosis, and lung infiltrates on imaging, suggesting autoimmune enteropathy complicated by infection. Conclusion: This report raises important questions regarding the clinical impact of heterozygous LRBA variant. It highlights the diagnostic value of WES in refractory cytopenias and inherited immune deficiencies. Abatacept, a CTLA-4-Ig fusion protein, is a promising targeted therapy for LRBA deficiency cases; yet its unavailability in Lebanon impeded its use, emphasizing the critical gap in access to targeted biologics in the MENA region.