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: Hidetoshi Takada, Masataka Ishimura, Tomohito Takimoto, Toaki Kohagura, Hideto Yoshikawa, Masue Imaizumi, Koichi Shichijyou, Yoko Shimabukuro, Tomoo Kise, Nobuyuki Hyakuna, Osamu Ohara, Shigeaki Nonoyama, Toshiro Hara
• Journal: Medicine (Medicine (Baltimore)) Vol. 95 Issue 4 Pg. e2437 (Jan 2016) ISSN: 1536-5964 [Electronic] United States
• PMID: 26825884 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Tumor Necrosis Factor-alpha
• IRAK4 protein, human
• Interleukin-1 Receptor-Associated Kinases

Topics

• Anti-Bacterial Agents (therapeutic use)
• Antibiotic Prophylaxis
• Child, Preschool
• Humans
• Immunologic Deficiency Syndromes (complications, genetics, immunology)
• Infant
• Infant Death
• Interleukin-1 Receptor-Associated Kinases (genetics, immunology)
• Meningitis, Pneumococcal (drug therapy, etiology, prevention & control)
• Monocytes (chemistry)
• Mutation
• Primary Immunodeficiency Diseases
• Time Factors
• Tumor Necrosis Factor-alpha (analysis)
• Umbilical Cord