title: Invasive Bacterial Infection in Patients with Interleukin-1 Receptor-associated Kinase 4 Deficiency: Case Report.
abstract: Interleukin-1 receptor-associated kinase 4 (IRAK4) deficiency (OMIM #607676) is a rare primary immunodeficiency of innate immune defect. We identified 10 patients from 6 families with IRAK4 deficiency in Japan, and analyzed the clinical characteristics of this disease. Nine patients had homozygous c.123_124insA mutation, and 1 patient had c.123_124insA and another nonsense mutation (547C>T). Umbilical cord separation occurred on the 14th day after birth or thereafter. Two patients had no severe infections owing to the prophylactic antibiotic treatment. Severe invasive bacterial infections occurred before the age of 3 in the other 8 patients. Among them, 7 patients had pneumococcal meningitis. Five patients died of invasive bacterial infection during infancy, although intravenous antibiotic treatment was started within 24 hours after onset in 4 patients among them. Analysis of cerebrospinal fluid of the patients who had fatal meningitis revealed very low glucose levels with only mild pleocytosis. The clinical courses of invasive bacterial infections were often rapidly progressive despite the early, appropriate antibiotic treatment in IRAK4 deficiency patients. The early diagnosis and appropriate prophylaxis of invasive bacterial infections are necessary for the patients.
authors.affiliation: From the Department of Perinatal and Pediatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan (HT); Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan (MI, TT, TH); Department of Pediatrics, Naha City Hospital, Naha, Japan (TK); Department of Pediatrics, Nagaoka Rehabilitation and Medical Center for Children, Nagaoka, Japan (HY); Department of Hematology and Oncology, Miyagi Children's Hospital, Sendai, Japan (MI); Department of Pediatrics, Tokushima Red Cross Hospital, Komatsushima, Japan (KS); Okinawa Prefectural Nanbu Medical Center and Children's Medical Center, Shimajiri-gun, Japan (YS, TK); Center of Bone Marrow Transplantation, Hospital of University of the Ryukyu, Nakagami-gun, Japan (NH); Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan (OO); and Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan (SN).
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Takada
authors.forename: Masataka
authors.initials: M
authors.lastname: Ishimura
authors.forename: Tomohito
authors.initials: T
authors.lastname: Takimoto
authors.forename: Toaki
authors.initials: T
authors.lastname: Kohagura
authors.forename: Hideto
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Masue
authors.initials: M
authors.lastname: Imaizumi
authors.forename: Koichi
authors.initials: K
authors.lastname: Shichijyou
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimabukuro
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kise
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hyakuna
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis; D002675:Child, Preschool; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000235:genetics / Q000276:immunology; D007223:Infant; D066088:Infant Death; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000276:immunology; D008586:Meningitis, Pneumococcal / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control*; D009000:Monocytes / Q000737:chemistry; D009154:Mutation; D000081207:Primary Immunodeficiency Diseases; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014470:Umbilical Cord
chemical_list: D000900:Anti-Bacterial Agents; D014409:Tumor Necrosis Factor-alpha; C507773:IRAK4 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases
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