title: IRAK-4 deficiency as a cause for familial fatal invasive infection by Streptococcus pneumoniae.
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.
authors.affiliation: Pediatric Intensive Care Unit, Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Serge
authors.initials: S
authors.lastname: Grazioli
authors.affiliation: Department of Medical Genetics, Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Hamilton
authors.affiliation: Department of Medical Genetics, Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: McKinnon
authors.affiliation: 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.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Del Bel
authors.affiliation: BC Centre for Disease Control Public Health Microbiology & Reference Laboratory, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Hoang
authors.affiliation: 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.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Cook
authors.affiliation: 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.
authors.forename: Kyla J
authors.initials: KJ
authors.lastname: Hildebrand
authors.affiliation: 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.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Junker
authors.affiliation: 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: sturvey@cw.bc.ca.
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Turvey
mesh_terms: D002675:Child, Preschool; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000235:genetics / Q000276:immunology*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000276:immunology; D008586:Meningitis, Pneumococcal / Q000209:etiology / Q000276:immunology*; D009154:Mutation; D010375:Pedigree; D000081207:Primary Immunodeficiency Diseases; D035781:Siblings; D013296:Streptococcus pneumoniae
chemical_list: C507773:IRAK4 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases
keywords: IRAK-4 deficiency; Invasive pneumococcal disease; Meningitis; Primary immunodeficiency; Streptococcus pneumoniae; Toll-like receptor signaling