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IRAK-4 deficiency is an inherited disorder of the immune system (primary immunodeficiency). This immunodeficiency leads to recurrent infections by a subset of bacteria known as pyogenic bacteria but not by other infectious agents. (Infection with pyogenic bacteria causes the production of pus.) The most common infections in IRAK-4 deficiency are caused by the Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. Most people with this condition have their first bacterial infection before age 2, and the infections can be life-threatening in infancy and childhood. Infections become less frequent with age.
Most people with IRAK-4 deficiency have invasive bacterial infections, which can involve the blood (septicemia), the membrane covering the brain and spinal cord (meningitis), or the joints (arthritis). Invasive infections can also cause areas of tissue breakdown and pus production (abscesses) on internal organs. In addition, affected individuals can have localized infections of the upper respiratory tract, skin, or eyes. Many people with IRAK-4 deficiency do not develop a high fever in response to these bacterial infections, even if the infection is severe.
IRAK-4 deficiency is a very rare condition, although the exact prevalence is unknown. At least 49 individuals with this condition have been described in the scientific literature.
IRAK-4 deficiency is caused by mutations in the IRAK4 gene, which provides instructions for making a protein that plays an important role in stimulating the immune system to respond to infection. The IRAK-4 protein is part of a signaling pathway that is involved in early recognition of foreign invaders (pathogens) and the initiation of inflammation to fight infection. This signaling pathway is part of the innate immune response, which is the body's early, nonspecific response to pathogens.
Mutations in the IRAK4 gene lead to the production of a nonfunctional protein or no protein at all. The loss of functional IRAK-4 protein blocks the initiation of inflammation in response to pathogens that would normally help fight the infections. Because the early immune response is insufficient, bacterial infections occur often and become severe and invasive.
Changes in this gene are associated with IRAK-4 deficiency.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
These resources address the diagnosis or management of IRAK-4 deficiency and may include treatment providers.
You might also find information on the diagnosis or management of IRAK-4 deficiency in Educational resources (http://ghr.nlm.nih.gov/condition/irak-4-deficiency/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/irak-4-deficiency/show/Patient+support).
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
You may find the following resources about IRAK-4 deficiency helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).
arthritis ; autosomal ; autosomal recessive ; bacteria ; breakdown ; cell ; deficiency ; fever ; gene ; immune response ; immune system ; immunodeficiency ; infection ; inflammation ; inherited ; kinase ; prevalence ; protein ; receptor ; recessive ; respiratory ; septicemia ; tissue
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.