背景:孟德尔对分枝杆菌疾病(MSMD)的易感性是一种罕见的临床综合征,其特征是对弱毒力分枝杆菌的易感性,包括卡介苗(BCG)疫苗和环境分枝杆菌。
目的:我们对遗传,免疫学,和报告的MSMD患者的临床发现。
方法:我们搜索了PubMed,WebofScience,和Scopus数据库,用于与MSMD有关的英文出版物。对所有全文进行了纳入资格评估。两名审稿人独立选择出版物,在有分歧的情况下,与第三位审查员协商。
结果:对其他资源的主要系统搜索和搜索确定了16,155篇文章。总的来说,来自63个国家的158篇文章被纳入定性和定量分析。总的来说,830名患者-436名男性(52.5%),369名女性(44.5%),对来自581个家庭的25例性别不详患者(3.0%)进行了评估。347例患者有阳性家族史(45.5%)。患者的平均年龄为10.41±0.42(平均值的标准误差)岁。MSMD的频率在伊朗最高,土耳其,沙特阿拉伯。淋巴结病是MSMD最常见的临床表现,报告378例(45.5%),多病灶35.1%。发烧,器官肿大,败血症是下一个最常见的发现,在251(30.2%)中报告,206(24.8%),和171例(20.8%),分别。总的来说,报告了21个已知与MSMD有关的基因中的299个独特突变:100个错义(34%),80插入-移码(插入或删除,27%),53个废话(18%),35个剪接位点(12%),10帧内(2.7%),6个indel(2%)和15个大缺失/重复突变。最后,报告的MSMD患者中有61%具有IL12RB1(41%)或IFNGR1(20%)的突变。在报告时,177名患者(21.3%)死亡,597人(71.9%)仍然活着。
结论:MSMD与高死亡率相关,主要是由于感染控制受损。曝光前策略,例如流行地区疫苗接种政策的变化,建立全球MSMD患者登记处,以及对受影响家庭的几代人的精确跟踪,似乎很重要,降低MSMD相关死亡率。
BACKGROUND: 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.
OBJECTIVE: We sought to perform a systematic
review of the genetic, immunologic, and clinical findings for reported patients with MSMD.
METHODS: 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.
RESULTS: 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 (SEM) 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 patients with MSMD had mutations of IL12RB1 (41%) or IFNGR1 (20%). At the time of the report, 177 of the patients (21.3%) were dead and 597 (71.9%) were still alive.
CONCLUSIONS: MSMD is associated with a high mortality rate, mostly due to impaired control of infection. Preexposure strategies, such as changes in vaccination policy in endemic areas, the establishment of a worldwide registry of patients with MSMD, and precise follow-up over generations in affected families, appear to be vital to decrease MSMD-related mortality.