IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease
Ku, Cheng-Lung × Picard, Capucine Erdös, Melinda Jeurissen, Axel Bustamante, Jacinta Puel, Anne von Bernuth, Horst Filipe-Santos, Orchidée Chang, Huey-Hsuan Lawrence, Tatiana Raes, Marc Maródi, László Bossuyt, Xavier Casanova, Jean-Laurent #
British Medical Association
Journal of Medical Genetics vol:44 issue:1 pages:16-23
BACKGROUND: About 2% of childhood episodes of invasive pneumococcal disease (IPD) are recurrent, and most remain unexplained. OBJECTIVE: To report two cases of otherwise healthy, unrelated children with recurrent IPD as the only clinical infectious manifestation of an inherited disorder in nuclear factor-kappaB(NF-kappaB)-dependent immunity. RESULTS: One child carried two germline mutations in IRAK4, and had impaired cellular responses to interleukin (IL)1 receptor and toll-like receptor (TLR) stimulation. The other child carried a hemizygous mutation in NEMO, associated with a broader impairment of NF-kappaB activation, with an impaired cellular response to IL-1R, TLR and tumour necrosis factor receptor stimulation. The two patients shared a narrow clinical phenotype, associated with two related but different genotypes. CONCLUSIONS: Otherwise healthy children with recurrent IPD should be explored for underlying primary immunodeficiencies affecting the IRAK4-dependent and NEMO-dependent signalling pathways.