D1.328 - CARD11 Dominant-Negative Mutation Presenting with Early Severe Bacterial Sepsis, Viral Susceptibility, and Alopecia Totalis in a Child

Dominant-negative mutations in CARD11 cause CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS), a heterogeneous inborn error of immunity that may present with infections, immune dysregulation, and atopy despite preserved baseline immunological parameters. We report a 7-year-old boy who first presented at 1 year of age with fulminant Clostridium septicum sepsis requiring laparotomy and bowel resection. He subsequently developed intermittent eczema and severe varicella infection complicated by alopecia totalis at 5 years of age. Growth and physical examination were otherwise unremarkable. Immunological evaluation demonstrated moderate neutropenia, normal IgG and IgM levels, elevated IgA, normal IgE, and normal T-, B-, and NK-cell subsets with preserved B-cell maturation. Vaccine assessment revealed impaired responses to pneumococcal polysaccharide antigens despite booster immunisation. T-cell proliferation was normal to phytohaemagglutinin but reduced following CD3/CD28 stimulation. Next-generation sequencing identified a heterozygous CARD11 c.128C>T (p.Thr43Met) variant, consistent with a dominant-negative effect on NF-κB signaling. The patient was commenced on azithromycin prophylaxis and remains under multidisciplinary follow-up. This case expands the clinical spectrum of CADINS, highlighting that severe early bacterial sepsis, viral susceptibility, and autoimmune manifestations such as alopecia may occur despite near-normal immunophenotyping, underscoring the importance of considering CARD11 defects in children with early severe infections and immune dysregulation.