Rare Ophthalmology News

Disease Profile

IRAK-4 deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

D84.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Interleukin receptor-associated kinase deficiency; IRAK4 deficiency

Categories

Congenital and Genetic Diseases; Immune System Diseases

Summary

IRAK-4 deficiency is a condition that affects the immune system (primary immunodeficiency). It causes recurring severe infections by a type of bacteria called pyogenic bacteria. Individuals with IRAK-4 deficiency seem to be particularly susceptible to infections caused by bacteria called Streptococcus pneumoniae. The deficiency is caused by mutations in the IRAK4 gene and is inherited in an autosomal recessive pattern. Treatment may include intravenous immunoglobulin therapy (IVIG), taking antibiotics before an infection develops, and vaccines. Althought the infections can be life-threatening, they tend to occur less often as a person gets older.[1][2]

Symptoms

Individuals with IRAK-4 deficiency are at increased risk of developing infections by bacteria such as Str. penumoniae, Staph. aureus, and P. aeruginosa. Most people with IRAK-4 deficiency start to develop infections by age 2. The infections can be difficult to diagnose because signs of inflammation don't appear right away. Individuals with IRAK-4 deficiency do not develop infections caused by viruses, parasites, or fungus. The condition seems to improve with age.[3][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Immunodeficiency
Decreased immune function
0002721
Neutropenia
Low blood neutrophil count
Low neutrophil count

[ more ]

0001875
Recurrent staphylococcal infections
0007499
Recurrent streptococcus pneumoniae infections
0005366
1%-4% of people have these symptoms
Increased circulating IgE level
0003212
Liver abscess
0100523
Recurrent streptococcal infections
0020096
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Transient neutropenia
0410255

Diagnosis

IRAK-4 deficiency can be diagnosed by very specific immune tests to determine if a person has an impaired response to most Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) agonists.[3] Genetic testing is also available for IRAK-4 deficiency and can be used to confirm the diagnosis.[1] The Genetic Testing Registry provides information on available genetic test for this condition. Because many laboratories do not accept direct contact from patients, we recommend that you work with your health care provider if you are interested in genetic testing.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss IRAK-4 deficiency. Click on the link to view a sample search on this topic.

          References

          1. Fischer A. Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency. Orphanet. 11/2006; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=70592. Accessed 9/20/2013.
          2. Picard C. Clinical Features and Outcome of Patients With IRAK-4 and MyD88 Deficiency. Medicine (Baltimore). 11/2010; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3103888/. Accessed 9/20/2013.
          3. Ku CL, von Bernuth H, Picard C, Zhang SY, Chang HC, Yang K et al. Selective predisposition to bacterial infections in IRAK-4–deficient children: IRAK-4–dependent TLRs are otherwise redundant in protective immunity. The Journal of Experimental Medicine. 10/01/2007; https://www.jem.org/cgi/content/full/204/10/2407. Accessed 9/20/2013.

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