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Case Reports
. 2007 Jan;44(1):16-23.
doi: 10.1136/jmg.2006.044446. Epub 2006 Sep 1.

IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease

Cheng-Lung Ku  1 , Capucine Picard, Melinda Erdös, Axel Jeurissen, Jacinta Bustamante, Anne Puel, Horst von Bernuth, Orchidée Filipe-Santos, Huey-Hsuan Chang, Tatiana Lawrence, Marc Raes, László Maródi, Xavier Bossuyt, Jean-Laurent Casanova
Affiliations
Case Reports

IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease

Cheng-Lung Ku et al. J Med Genet. 2007 Jan.

Abstract

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.

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Conflict of interest statement

Competing interests: XB is a senior clinical investigator of the Fund for Scientific Research—Flanders. J‐LC is an International Scholar of the Howard Hughes Medical Institute.

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