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Disease Profile

IL12RB1 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.

Unknown

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)

Mendelian susceptibility to mycobacterial infections due to IL12 deficiency; IL-12Râ1 deficiency; Mendelian susceptibility to interleukin 12 receptor beta 1 deficiency;

Categories

Congenital and Genetic Diseases; Immune System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 319552

Definition
Mendelian susceptibility to mycobacterial diseases (MSMD) due to complete interleukin-12 receptor subunit beta-1 (IL12RB1) deficiency is a genetic variant of MSMD (see this term) characterized by mild bacillus Calmette-Guérin (BCG) infections and recurrent Salmonella infections.

Epidemiology
The prevalence is unknown. Over 140 cases have been reported in the world.

Clinical description
Disease onset usually occurs in patients before the age of 12 with the appearance of BCG disease, usually after receiving the vaccination. Over half of patients with this variant experience an additional infection with non-typhoidal Salmonella. Severe tuberculosis caused by Mycobacterium tuberculosis has been reported in several unrelated patients, providing the first documented evidence of a mendelian predisposition to tuberculosis. Other infections with Paracoccidiodes brasiliensis, Leishmania and Klebsiella have been reported in a single patient. Some patients also suffer from Candida infections. Most genetically affected siblings of index cases are asymptomatic, indicating low penetrance for case definition phenotypes.

Etiology
MSMD due to complete IL12RB1 deficiency is caused by mutations in the IL12RB1 gene (19p13.1) subunit that encodes for the IL-12R-beta1 chain. These mutations impair the IL-12/IL-23 pathway essential for production of IFN-beta and the resulting immunity against Salmonella and BCG infections. Two clinically indistinguishable forms have been reported defined by the presence or absence of protein expression on the cell surface.

Diagnostic methods
Diagnosis is made by laboratory analysis. In general, there is no expression of IL12RB1 at the surface of activated Tlymphocytes and NK cells. For the moment, only one mutation of IL12 RB1 leads to residual expression of the receptor on the cell surface. Low IFN-gamma levels are measured by ELISA after whole blood activation by BCG and BCG+IL-12. Genetic testing reveals mutations in IL12RB1. Impaired development of the Th17 cells is demonstrated in patients with this immunodeficiency.

Differential diagnosis
Other genetic etiologies of MSMD should be excluded.

Antenatal diagnosis
This immunodeficiency is not severe and antenatal diagnosis is not necessary.

Genetic counseling
MSMD due to complete IL12RB1 deficiency is inherited in an autosomal recessive manner so genetic counseling is possible.

Management and treatment
BCG vaccination should be avoided in those with a known mutation in the IL12RB1 gene. Treatment is usually attained from long term antimicrobial therapy combined with recombinant IFN-gamma. For those who have localized splenic/mesenteric lesions with poor drug penetration, surgical removal is indicated.

Prognosis
With proper treatment the prognosis is usually good with most patients reaching adulthood.

Visit the Orphanet disease page for more resources.

Symptoms

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
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Immunodeficiency
Decreased immune function
0002721
Recurrent mycobacterial infections
0011274

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.

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 IL12RB1 deficiency. Click on the link to view a sample search on this topic.