IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease
CL Ku, C Picard, M Erdös, A Jeurissen… - Journal of medical …, 2007 - jmg.bmj.com
CL Ku, C Picard, M Erdös, A Jeurissen, J Bustamante, A Puel, H von Bernuth…
Journal of medical genetics, 2007•jmg.bmj.comBackground: 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-κB (NF-κB)-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 …
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-κB (NF-κB)-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 …
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-κB(NF-κB)-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-κB 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.
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