Tuberculosis

Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis. While TB is primarily an infectious disease rather than a genetic disorder, certain rare forms of susceptibility to mycobacterial infections have a genetic basis, which is why it appears in rare disease registries. Mendelian susceptibility to mycobacterial diseases (MSMD) encompasses a group of rare genetic conditions in which affected individuals are highly vulnerable to infections by weakly virulent mycobacteria, including the TB bacillus and BCG vaccine strains. TB most commonly affects the lungs (pulmonary tuberculosis) but can also involve virtually any organ system, including the lymph nodes, bones, joints, kidneys, central nervous system, and gastrointestinal tract (extrapulmonary tuberculosis). ICD-10 codes A15 and A16 specifically refer to respiratory tuberculosis. Key symptoms of pulmonary TB include chronic cough (often lasting more than three weeks), hemoptysis (coughing up blood), fever, night sweats, weight loss, fatigue, and chest pain. Extrapulmonary forms may present with lymphadenopathy, bone pain, meningitis, or organ-specific symptoms depending on the site of infection. Latent TB infection may be entirely asymptomatic. In the context of genetic susceptibility (MSMD), patients may present with unusually severe, disseminated, or recurrent mycobacterial infections, often beginning in childhood. Mutations in genes involved in the IL-12/IFN-gamma signaling axis, including IFNGR1, IFNGR2, IL12B, IL12RB1, STAT1, IRF8, ISG15, and others, have been identified as causes of increased susceptibility. Treatment of active TB typically involves a multi-drug regimen consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol for an initial intensive phase of two months, followed by a continuation phase of isoniazid and rifampicin for four months. Drug-resistant TB requires longer and more complex treatment regimens. For patients with genetic susceptibility to mycobacterial disease, adjunctive therapy with recombinant interferon-gamma (IFN-γ) may be beneficial. Hematopoietic stem cell transplantation has been considered in severe cases of MSMD. Early diagnosis and appropriate treatment are essential to prevent complications and transmission.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Tuberculosis