Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency

What it is

From: Orphanet

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

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal circulating interleukin concentration · Very frequent (99-80%)

The concentration of an interleukin (a class of cytokines) is outside the limits of normal.

BCGosis · Very frequent (99-80%)

Distant, or disseminated infection with Bacillus Calmette-Guerin (BCG) following vaccination associated with failure to contain thebacillus Calmette-Guerin (BCG) following vaccination leading to spread of BCG to many sites in the body. The tuberculosis vaccine BCG contains live attenuated Mycobacterium bovis.

Immunodeficiency · Very frequent (99-80%)

Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.

Recurrent mycobacterial infections · Very frequent (99-80%)

Increased susceptibility to mycobacterial infections as manifested by recurrent episodes of mycobacterial infection.

Disseminated nontuberculous mycobacterial infection · Frequent (79-30%)

Disseminated infection with non-tuberculous mycobacteria (NTM), involving multiple organ systems that occurs in the context of immune deficiency.

Lymphadenitis · Frequent (79-30%)

Inflammation of a lymph node.

Recurrent candida infections · Frequent (79-30%)

Increased susceptibility to Candida infections as manifested by recurrent episodes of Candida infection.

Pneumonia · Occasional (29-5%)

Inflammation of any part of the lung parenchyma.

Salmonella osteomyelitis · Occasional (29-5%)

Osteomyelitis caused by infection with the bacteria, salmonella.

Tegumentary leishmaniasis susceptibility · Occasional (29-5%)

Increased susceptibility to infection by the protozan parasite of the genus Leishmania.

Coccidioidomycosis · Very rare (<4-1%)

Infection by a Coccidioides species fungus. These are dimorphic, soil-dwelling, fungi known to cause a broad spectrum of disease, ranging from a mild febrile illness to severe pulmonary manifestations or disseminated disease. The genus Coccidioides is comprised of two genetically distinct species: Coccidioides immitis and C. posadasii.

Histoplasmosis · Very rare (<4-1%)

An increased susceptibility to Histoplasma capsulatum infections as manifested by a recurrent or severe/invasive infection with Histoplasma capsulatum, or occurring in an unusual anatomical location.

Recurrent Klebsiella infections · Very rare (<4-1%)

Increased susceptibility to Klebsiella infections as manifested by recurrent episodes of Klebsiella infection.

Severe toxoplasmosis · Very rare (<4-1%)

Toxoplasmosis is a widespread parasitic infection that is frequently asymptomatic in immunocompetent patients. However, this obligate intracellular protozoan parasite can evade the immune system and persist for the life of its host in cyst form, predominantly in the brain, retina, and muscles. Reactivation of latent cysts may occur when the immune system fails to maintain cytokine pressure, which mainly relies on gamma interferon (IFN-gamma). Toxoplasmosis is a life-threatening infection in immunocompromised patients (ICPs).

Other findings in the same source

From: Orphanet

Additional reported features include Vasculitis in the skin (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Childhood

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Reported case(s): 180.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency is Allergy and Immunology, with a allergist / clinical immunologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the history suggest an allergy, an immune problem or another explanation?
• How would any proposed allergy or immune test change care?
• Is an individual emergency plan needed, and who should understand it?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.