Case report: A novel IKBKB variant (c.1705G>T) is associated with immune dysregulation and disseminated tuberculosis.

Gabriel Emmanuel Arce-Estrada ¹ Miguel Rodríguez-Morales ² Selma Cecilia Scheffler-Mendoza ³ LAURA BERRON RUIZ ¹ Sara Elva Espinosa-Padilla ^1* Francisco Alberto Contreras-Verduzco ^1,4*

• ¹ Unidad de Investigación en Inmunodeficiencias, Instituto Nacional de Pediatria, Mexico City, México, Mexico
• ² Faculty of Medicine, National Autonomous University of Mexico, Mexico City, México, Mexico
• ³ Immunology Service, National Institute of Pediatrics (Mexico), Mexico City, México, Mexico
• ⁴ National Institute of Pediatrics (Mexico), Mexico City, Mexico

Objective: To describe a novel IKBKB variant linked to immune dysregulation and disseminated tuberculosis, alongside a review of pathogenic variants to outline their phenotypic spectrum.Material and methods: Observational case report and literature review.Results: A five-month-old girl from an endogamous Mexican population developed symptoms suggestive of Kawasaki disease which progressed to hemophagocytic syndrome. Mycobacterium bovis was found in her skin, blood, and bone marrow. She had received the Bacillus Calmette-Guérin (BCG) vaccine on the second day of life. Genetic testing revealed a homozygous pathogenic variant (PV) in the IKBKB gene (c.1705G>T, p.Glu569*). Both parents were heterozygous. Fourteen publications were found, encompassing 33 patients with 14 different PV, including the case described in this work. Discussion: Hypogammaglobulinemia, candidiasis and mycobacterial infections were common in most cases identified. Our case is unique in presenting with Kawasaki disease, hemophagocytic syndrome, and mycobacteria from skin, blood, and bone marrow.Conclusions: We identified a novel homozygous PV in the IKBKB gene, highlighting new clinical manifestations.