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J Med Genet. 2007 Jan;44(1):16-23. Epub 2006 Sep 1.

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

Author information

1
Laboratory of Human Genetics of Infectious Diseases, Necker Medical School, University of Paris René Descartes, Paris, France.

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.

PMID:
16950813
PMCID:
PMC2597905
DOI:
10.1136/jmg.2006.044446
[Indexed for MEDLINE]
Free PMC Article

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