IRAK-4 deficiency as a cause for familial fatal invasive infection by Streptococcus pneumoniae

Serge Grazioli; Sara J Hamilton; Margaret L McKinnon; Kate L Del Bel; Linda Hoang; Victoria E Cook; Kyla J Hildebrand; Anne K Junker; Stuart E Turvey

doi:10.1016/j.clim.2015.12.007

IRAK-4 deficiency as a cause for familial fatal invasive infection by Streptococcus pneumoniae

Clin Immunol. 2016 Feb:163:14-6. doi: 10.1016/j.clim.2015.12.007. Epub 2015 Dec 15.

Authors

Serge Grazioli¹, Sara J Hamilton², Margaret L McKinnon², Kate L Del Bel³, Linda Hoang⁴, Victoria E Cook³, Kyla J Hildebrand³, Anne K Junker³, Stuart E Turvey⁵

Affiliations

¹ Pediatric Intensive Care Unit, Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
² Department of Medical Genetics, Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
³ Division of Allergy and Clinical Immunology, Department of Pediatrics, British Columbia Children's Hospital and Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
⁴ BC Centre for Disease Control Public Health Microbiology & Reference Laboratory, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
⁵ Division of Allergy and Clinical Immunology, Department of Pediatrics, British Columbia Children's Hospital and Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada. Electronic address: [email protected].

PMID: 26698383
DOI: 10.1016/j.clim.2015.12.007

Abstract

In this Letter to the Editor we report the case of two siblings with fatal pneumococcal meningitis as the initial manifestation of IRAK-4 deficiency caused by previously undescribed mutations in IRAK4. The letter also highlights the importance of invasive pneumococcal infection as a critical 'red flag' warning of the potential for an underlying primary immunodeficiency and identifies some of the challenges in making the clinical diagnosis of IRAK-4 deficiency.

Keywords: IRAK-4 deficiency; Invasive pneumococcal disease; Meningitis; Primary immunodeficiency; Streptococcus pneumoniae; Toll-like receptor signaling.

Publication types

Case Reports
Letter

MeSH terms

Child, Preschool
Fatal Outcome
Female
Humans
Immunologic Deficiency Syndromes / complications
Immunologic Deficiency Syndromes / genetics
Immunologic Deficiency Syndromes / immunology*
Interleukin-1 Receptor-Associated Kinases / genetics
Interleukin-1 Receptor-Associated Kinases / immunology
Meningitis, Pneumococcal / etiology
Meningitis, Pneumococcal / immunology*
Mutation
Pedigree
Primary Immunodeficiency Diseases
Siblings
Streptococcus pneumoniae

Substances

IRAK4 protein, human
Interleukin-1 Receptor-Associated Kinases

Supplementary concepts

IRAK4 Deficiency