Poznan University of Medical Sciences

Monoallelic variants in the nuclear factor kappa B 1 (NFKB1) gene reinforce the functional haploinsufficiency causing immunodeficiency with marked individual and intrafamilial variability in genotype-phenotype correlations. The leading clinical manifestations of NF-κB1 deficiency are recurrent infections and immune dysregulation disorders with autoinflammatory and lymphoproliferative disease. The reported patient initially presented with a neonatal sepsis-like illness with meningitis because of a parechovirus infection. The diagnosis of an inborn error of immunity, common variable immunodeficiency (CVID), was established based on hypogammaglobulinemia, impaired antibody response to vaccines, IgG subclass deficiency, and low numbers of switched memory B cells. Molecular genetic testing using trio whole exome sequencing was done to define the background of the presenting phenotype, and it revealed a novel heterozygous variant of NFKB1. Viral meningitis and sepsis-like illness are unusual, previously unreported, infectious complications in NF-κB1 deficiency. The transcriptional NF-κB1 regulatory effect on different target gene repertoires and numerous processes including immune and inflammatory responses may indicate the vulnerability of deficient patients to severe viral infections. This case report exemplifies the advancement of immunogenetics paving the way for the transition from the initial era of clinical recognition to the era of molecular diagnosis of the pediatric CVID.