Mendelian susceptibility to mycobacterial disease: a rare genetic disorder that demands attention

Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a rare primary immunodeficiency characterized by increased susceptibility to infections caused by weakly virulent mycobacteria and other intracellular pathogens. MSMD is caused by inborn Query ID="Q1" Text="Affiliations: Kindly check and confirm the processed affiliations are correct and amend if any." errors in the interleukin-12/interferon-gamma (IL-12/IFN-γ) axis, crucial for immunity against mycobacteria. To date, mutations in over 20 genes have been identified, affecting various components of this pathway. Diagnosis of MSMD involves a multifaceted approach, combining clinical assessment, microbiological investigations, immunological assays, and genetic testing. Advanced genetic technologies, including next-generation sequencing, have significantly improved diagnostic capabilities, although challenges remain in identifying causative mutations in all cases. Management of MSMD patients requires individualized strategies based on the specific genetic defect and clinical presentation. Treatment approaches include antimicrobial therapy, immunomodulation with IFN-γ, hematopoietic stem cell transplantation, and emerging gene therapy techniques. Despite these advances, optimal management of MSMD patients, particularly those with severe phenotypes, remains challenging. This review provides a comprehensive overview of MSMD, focusing on its genetic basis, clinical manifestations, diagnostic approaches, and treatment strategies. This review also highlights current research trends and future directions in MSMD, including efforts to identify novel genetic causes, develop more accurate diagnostic tools, and explore innovative therapeutic approaches. The potential of gene editing technologies and personalized medicine offers promising avenues for improving patient outcomes.