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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.

References

    1. Wong W Y, Overturf G D, Powars D R. Infection caused by Streptococcus pneumoniae in children with sickle cell disease: epidemiology, immunologic mechanisms, prophylaxis, and vaccination. Clin Infect Dis 1992141124–1136. - PubMed
    1. Picard C, Puel A, Ku C L, Casanova J L. Primary immunodeficiencies associated with pneumococcal disease. Curr. Opin. Allergy Clin. Immunol 20033451–459. - PubMed
    1. Doffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, Bodemer C, Kenwrick S, Dupuis‐Girod S, Blanche S, Wood P, Rabia S H, Headon D J, Overbeek P A, Le Deist F, Holland S M, Belani K, Kumararatne D S, Fischer A, Shapiro R, Conley M E, Reimund E, Kalhoff H, Abinun M, Munnich A, Israel A, Courtois G, Casanova J L. X‐linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF‐kappaB signaling. Nat Genet 200127277–285. - PubMed
    1. Picard C, Puel A, Bonnet M, Ku C L, Bustamante J, Yang K, Soudais C, Dupuis S, Feinberg J, Fieschi C, Elbim C, Hitchcock R, Lammas D, Davies G, Al‐Ghonaium A, Al‐Rayes H, Al‐Jumaah S, Al‐Hajjar S, Al‐Mohsen I Z, Frayha H H, Rucker R, Hawn T R, Aderem A, Tufenkeji H, Haraguchi S, Day N K, Good R A, Gougerot‐Pocidalo M A, Ozinsky A, Casanova J L. Pyogenic bacterial infections in humans with IRAK‐4 deficiency. Science 20032992076–2079. - PubMed
    1. Puel A, Picard C, Ku C L, Smahi A, Casanova J L. Inherited disorders of NF‐kappaB‐mediated immunity in man. Curr Opin Immunol 20041634–41. - PubMed

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