Mendelian susceptibility to atypical mycobacteria

Mendelian Susceptibility to Mycobacterial Diseases (MSMD) is a rare genetic disorder characterized by a predisposition to infections caused by weakly virulent mycobacteria, such as Mycobacterium avium and Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccines, as well as non-mycobacterial infections with pathogens like Salmonella. This condition is a prime example of the critical role that the immune system plays in protecting the body against certain types of bacteria. MSMD is considered a primary immunodeficiency disorder, highlighting a specific defect within the immune response to these pathogens.

Etiology[edit | edit source]

MSMD is caused by mutations in genes that are crucial for the interferon-gamma (IFN-γ) signaling pathway, a key component of the immune response to mycobacterial infections. To date, mutations in at least ten genes (e.g., IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, IRF8, and others) have been identified to cause various forms of MSMD. These mutations can be inherited in an autosomal recessive, autosomal dominant, or X-linked manner, depending on the gene involved.

Clinical Presentation[edit | edit source]

Individuals with MSMD typically present in childhood with clinical signs and symptoms following vaccination with the BCG vaccine or exposure to environmental mycobacteria. Clinical manifestations may include localized lymphadenitis (swelling of the lymph nodes), osteomyelitis (infection in the bone), or disseminated disease, which can be life-threatening. Infections caused by non-mycobacterial pathogens, such as Salmonella, can also occur.

Diagnosis[edit | edit source]

The diagnosis of MSMD is based on the clinical presentation, family history, and laboratory findings. Laboratory tests may reveal an absence or dysfunction of the IFN-γ signaling pathway. Genetic testing is crucial for identifying the specific mutation(s) responsible for the disorder, which can guide treatment decisions and genetic counseling.

Treatment[edit | edit source]

Management of MSMD focuses on treating infections with appropriate antibiotics and preventing future infections. Prophylactic antibiotics may be recommended for some individuals to prevent recurrent infections. In cases where a specific genetic defect is identified, hematopoietic stem cell transplantation (HSCT) may be considered as a potential cure. Additionally, recombinant IFN-γ therapy has been used in some cases to boost the immune response to mycobacterial infections.

Prognosis[edit | edit source]

The prognosis for individuals with MSMD varies depending on the severity of the disease and the specific genetic defect. Early diagnosis and appropriate management can significantly improve outcomes. However, without treatment, recurrent infections can lead to significant morbidity and mortality.