B cell Expansion with NF-κB Activation and T cell Anergy (BENTA) disease is a rare inborn error of immunity caused by gain-of-function (GOF) variants in CARD11. It is characterized by early-onset lymphadenopathy, splenomegaly, and profound polyclonal B cell lymphocytosis, with recurrent infections and immune dysregulation.
We report a full-term female infant initially admitted with indirect hyperbilirubinemia, thrombocytopenia, and mild splenomegaly. At 6 months of age, she was hospitalized with fever, bilateral facial swelling, otomastoiditis, and urinary tract infection. Laboratory evaluation showed leukocytosis with progressive B cell lymphocytosis and evolving cytopenia with a positive direct Coombs test. Persistent splenomegaly and cervical lymphadenopathy were noted on the follow-up visit. Family history was significant for parental consanguinity and an older sibling with chronic mucocutaneous candidiasis and poor growth. Whole-exome sequencing identified a pathogenic missense variant in CARD11 (c.146G>A, p.Cys49Tyr), previously reported to cause BENTA disease due to a gain-of-function mechanism. During a subsequent admission. Her immunological evaluation showed marked lymphocytosis (absolute lymphocyte count [ALC] 51 × 109/L), increased CD19+ B cells (12,309/µL), and reduced CD3+ T cells (3,196/µL), including CD4+ 1,846/µL and CD8+ 1,208/µL. Double-negative T cells were elevated (6.3%), and natural killer (NK) cells were low (CD16+/56+ 180/µL). IgG 9.8 g/L, IgM 2.4 g/L, IgA 0.3 g/L, and total IgE <15. Tetanus antitoxin 0.25 IU/mL, diphtheria antibodies 0.02 IU/mL. Initially, she was clinically stable, but then she developed pancytopenia with Hgb 7 g/dL, platelets 30 × 109/L, absolute neutrophil count [ANC] 0.37 × 109/L, and ALC 10 × 109/L. EBV and hemophagocytic lymphohistiocytosis (HLH) were excluded, and she received intravenous immunoglobulin on two occasions. After discharge, the family stopped following up with the immunology clinic and elected to see traditional medicine. When they returned four months later, the patient had worsening lymphadenopathy and splenomegaly, along with more than twenty healed cautery marks on the abdomen. Plans for evaluation of B cell malignancy risk, initiation of sirolimus, and referral for hematopoietic stem cell transplantation were all declined by the family.
This case illustrates an early-severe phenotype of BENTA disease associated with significant lymphoproliferation, autoimmune cytopenia, and recurrent infections. It emphasizes the importance of early recognition and proactive management, while highlighting the impact of treatment refusal on patient outcomes.
