Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency

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ORPHA:319547OMIM:614889D84.8
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Overview

Mendelian susceptibility to mycobacterial diseases due to complete interferon-gamma receptor 2 (IFNγR2) deficiency is a very rare inherited immune disorder. In this condition, the body's immune system cannot properly respond to a signaling molecule called interferon-gamma, which plays a critical role in fighting infections caused by mycobacteria. Mycobacteria include the germs that cause tuberculosis (TB) as well as other normally harmless environmental bacteria (called nontuberculous mycobacteria or NTM). Because the receptor for interferon-gamma is completely missing or nonfunctional, the immune system cannot activate certain white blood cells (macrophages) to kill these germs effectively. Children with this condition typically become severely ill in infancy or early childhood after exposure to mycobacteria, including after receiving the BCG vaccine (a live vaccine against tuberculosis given in many countries). Infections can spread throughout the body, affecting the lungs, lymph nodes, bones, skin, and other organs. These infections are often life-threatening and very difficult to treat with antibiotics alone. The treatment landscape for complete IFNγR2 deficiency is challenging. Standard antibiotic therapy for mycobacterial infections is often insufficient because the underlying immune defect remains. Hematopoietic stem cell transplantation (bone marrow transplant) is currently the only potentially curative treatment, though it carries significant risks. Without transplant, patients face recurrent and severe infections throughout life. Gene therapy is being explored as a future option but is not yet available as a standard treatment.

Also known as:

Key symptoms:

Severe infections from normally harmless environmental bacteria (mycobacteria)Severe reaction to BCG vaccinationWidespread (disseminated) tuberculosis or mycobacterial infectionSwollen lymph nodes that do not improve with treatmentPersistent high feversChronic cough and lung infectionsWeight loss and failure to thriveBone infections (osteomyelitis)Skin lesions or abscessesEnlarged liver or spleenRecurrent infections despite antibiotic treatmentInfections caused by Salmonella bacteriaPoor growth in infancy and childhood

Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Infantile

Begins in infancy, roughly 1 month to 2 years old

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency.

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No specialists are currently listed for Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency.

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Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency.

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Community

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Caregiver Resources

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Questions for your doctor

Bring these to your next appointment

  • Q1.Is my child a candidate for bone marrow transplant, and when should it be considered?,What antibiotics will my child need, and for how long?,How can we best protect my child from mycobacterial infections in daily life?,Are there any vaccines my child should avoid, and which ones are safe?,Should other family members be tested for this genetic condition?,What are the signs of a new infection that should prompt an emergency visit?,Are there any clinical trials or new treatments being studied for this condition?

Common questions about Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency

What is Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency?

Mendelian susceptibility to mycobacterial diseases due to complete interferon-gamma receptor 2 (IFNγR2) deficiency is a very rare inherited immune disorder. In this condition, the body's immune system cannot properly respond to a signaling molecule called interferon-gamma, which plays a critical role in fighting infections caused by mycobacteria. Mycobacteria include the germs that cause tuberculosis (TB) as well as other normally harmless environmental bacteria (called nontuberculous mycobacteria or NTM). Because the receptor for interferon-gamma is completely missing or nonfunctional, the im

How is Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency inherited?

Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency typically begin?

Typical onset of Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency is infantile. Age of onset can vary across affected individuals.