Mendelian Susceptibility to Mycobacterial Disease: Retrospective clinical and genetic study in Mexico.

Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a defect in intrinsic and innate immunity characterized by selective susceptibility to clinical diseases caused by Mycobacteria.
We aimed to describe the biggest cohort of Mexican patients with MSMD published so far.
This is an observational, retrospective, and descriptive study where we present 22 cases of MSMD. We performed immunological analyses including NADPH oxidase activity, cellular expression of IL-12RB1, IFN-gR1, IFN-gR2, and the phenotyping of peripheral blood lymphocyte subsets. The genetic diagnoses were made using Sanger sequencing, next-generation sequencing, or whole-exome sequencing.
Because the Bacillus Calmette–Guérin vaccination is mandatory at birth in Mexico, presentation differs from cohorts published by other countries. In Mexican patients the first clinical manifestation is infection by BCG and appears at 6 months of age on average, with 5 months being the average timespan between the application of the vaccine and the development of the infection. Despite its early clinical manifestations, it was at the age of 4.5 years and above that the clinical diagnosis was made, and it still took another 4 years on average to provide a genetic diagnosis. The pathogenic variant more commonly presented was the defect in the IL12RB1 gene, followed by pathogenic variants in the IFNGR1 and IFNGR2 genes.
Furthermore, not only Mycobacteria affect these patients, but intracellular pathogens like Salmonella, Candida, Paracoccidioidomyces, Histoplasma and different kind of viruses can also cause life-threating conditions.
MSMD is not well-recognized by many physicians, even though mycobacterial infections are endemic in Mexico, and unfortunately this pathology is underdiagnosed or has a delayed diagnosis. We must raise awareness on inborn errors of immunity in first contact physicians. If we face an infant suffering adverse reactions to the BCG vaccine or severe infections caused by intracellular pathogens, we must rule MSMD out.

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