Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare clinical syndrome characterized by vulnerability to weakly virulent mycobacterial species, including Bacillus Calmette-Guérin (BCG) vaccines and environmental mycobacteria. We performed a systematic review of the genetic, immunological, and clinical findings for reported MSMD patients. We searched PubMed, Web of Science, and Scopus databases for publications in English relating to MSMD. All full texts were evaluated for eligibility for inclusion. Two reviewers independently selected the publications, with a third reviewer consulted in cases of disagreement. A primary systematic search and searches of other resources identified 16,155 articles. In total, 158 articles from 63 countries were included in qualitative and quantitative analyses. In total, 830 patients — 436 males (52.5%), 369 females (44.5%), and 25 patients of unknown sex (3.0%) — from 581 families were evaluated. A positive family history was reported in 347 patients (45.5%). The patients had a mean age of 10.41 ± 0.42 (standard error of the mean) years. The frequency of MSMD was highest in Iran, Turkey, and Saudi Arabia. Lymphadenopathy was the most common clinical manifestation of MSMD, reported in 378 (45.5%) cases and multifocal in 35.1%. Fever, organomegaly, and sepsis were the next most frequent findings, reported in 251 (30.2%), 206 (24.8%), and 171 (20.8%) cases, respectively. In total, 299 unique mutations in 21 genes known to be involved in MSMD were reported: 100 missense (34%), 80 indel-frameshift (insertion or deletion, 27%), 53 nonsense (18%), 35 splice site (12%), 10 indel-in frame (2.7%), 6 indel (2%) and 15 large deletion/duplication mutations. Finally, 61% of the reported MSMD patients had mutations of (41%) or (20%). At the time of the report, 177 of the patients (21.3%) were dead, and 597 (71.9%) were still alive. MSMD is associated with a high mortality rate, mostly due to impaired control of infection. Pre-exposure strategies, such as changes in vaccination policy in endemic areas, the establishment of a worldwide registry of MSMD patients, and precise follow-up over generations in affected families, appear to be vital, to decrease MSMD-related mortality.

中文翻译：

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830 名孟德尔分枝杆菌疾病 (MSMD) 易感性患者的遗传、免疫学和临床特征：系统评价

孟德尔分枝杆菌疾病易感性 (MSMD) 是一种罕见的临床综合征，其特征是易受弱毒力分枝杆菌物种的影响，包括卡介苗 (BCG) 疫苗和环境分枝杆菌。我们对报告的 MSMD 患者的遗传、免疫学和临床结果进行了系统回顾。我们检索了 PubMed、Web of Science 和 Scopus 数据库，查找与 MSMD 相关的英文出版物。对所有全文的纳入资格进行了评估。两名审稿人独立选择出版物，如有分歧，则咨询第三名审稿人。初步系统搜索和其他资源搜索确定了 16,155 篇文章。总共有来自 63 个国家的 158 篇文章被纳入定性和定量分析。总共有来自 581 个家庭的 830 名患者接受了评估，其中包括 436 名男性 (52.5%)、369 名女性 (44.5%) 和 25 名性别未知的患者 (3.0%)。347 名患者 (45.5%) 报告有阳性家族史。患者的平均年龄为 10.41 ± 0.42（平均值标准误）岁。MSMD 的发病率在伊朗、土耳其和沙特阿拉伯最高。淋巴结肿大是 MSMD 最常见的临床表现，有 378 例 (45.5%) 病例报告，其中 35.1% 为多灶性。其次是发热、器官肿大和败血症，分别有 251 例 (30.2%)、206 例 (24.8%) 和 171 例 (20.8%) 病例报告。总共报告了 21 个已知与 MSMD 相关的基因中的 299 个独特突变：100 个错义（34%）、80 个插入或移码（插入或删除，27%）、53 个无义（18%）、35 个剪接位点（12 %)、10 个插入缺失框架 (2.7%)、6 个插入缺失 (2%) 和 15 个大缺失/重复突变。最后，61% 报告的 MSMD 患者有 (41%) 或 (20%) 的突变。截至报告发布时，177 名患者（21.3%）死亡，597 名患者（71.9%）仍活着。MSMD 与高死亡率相关，主要是由于感染控制受损。暴露前策略，例如改变流行地区的疫苗接种政策、建立全球 MSMD 患者登记册以及对受影响家庭的几代人进行精确随访，对于降低 MSMD 相关死亡率似乎至关重要。