Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis-Bacillus Calmette-Guerin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 (n = 13), IFNGR1 (n = 3), and IFNGR2 (n = 1) genes. Interleukin-12R beta 1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.

Automated summary

This study reviewed the clinical, immunological, and genetic characteristics of MSMD patients in Mexico and identified IL12RB1 gene defect as the main cause of MSMD in the cohort. BCG infection was found to be the primary cause of morbidity and mortality in these patients.