Epidemiological and genetic features of amyotrophic lateral sclerosis in Latin America and the Caribbean: a systematic review

Introduction: Heterogeneity of amyotrophic lateral sclerosis (ALS) has been suggested in terms of epidemiology, phenotypes and genetics between geographic areas and populations. However, there is limited information in Latin America. We conducted a systematic review that aimed to describe the epidemiology, frequency of genetic mutations, clinical characteristics and survival of ALS patients in this region. Methods: We reviewed Medline, Scopus, Scielo and LILACS databases up to April 2020. The search terms “Amyotrophic Lateral Sclerosis” or “Motor Neuron Disease” were used in combination with the list of Latin American countries from the United Nations. All observational studies were included. A methodological overview was performed using the principles of descriptive epidemiology. Results: Overall, 1364 publications were identified and 36 studies were selected, covering 13 Latin American countries. According to the original reports, ALS occurrence varied among countries with a standardized incidence ranging from 0.3 per 100,000 person-years follow up (PYFU) in Ecuador to 3.6 per 100,000 PYFU in Uruguay. A low proportion of the C9orf72 repeat expansion was reported in Cuba and Brazil. We identified age at onset between 50 and 60 years. Survival time was higher than 40 months in half of the studies. Data from multiethnic populations reported a higher risk of developing ALS in Caucasians compared to admixed and Black populations. Conclusion: This review provides a perspective of ALS variability across Latin America and highlights specific differences when comparing to Europe and North America. However, we cannot draw firm conclusions because of different methodological concerns within the studies.

引言：已有研究表明，肌萎缩侧索硬化症（Amyotrophic Lateral Sclerosis, ALS）在不同地理区域与人群之间，在流行病学特征、表型及遗传学层面均存在异质性。但目前拉丁美洲地区的相关研究数据仍较为匮乏。本研究开展了一项系统综述，旨在阐明该区域ALS患者的流行病学特征、基因突变发生频率、临床特点及生存情况。方法：本研究检索了截至2020年4月的Medline、Scopus、SciELO及LILACS数据库。检索策略以“肌萎缩侧索硬化症”或“运动神经元病”为关键词，并结合联合国拉丁美洲国家名录进行组合检索。本研究纳入所有观察性研究，并依据描述流行病学原则开展方法学概述。结果：本研究共检索到1364篇文献，最终纳入36项研究，覆盖拉丁美洲13个国家。基于原始研究报告，不同国家的ALS发病情况存在差异：标化发病率范围为厄瓜多尔的0.3/10万人年随访（person-years follow up, PYFU）至乌拉圭的3.6/10万人年随访。古巴与巴西的研究显示，C9orf72基因重复扩增的检出比例较低。本研究发现患者的发病年龄集中于50~60岁区间。半数纳入研究的患者生存时间超过40个月。多民族人群相关数据显示，与混血人群及黑人人群相比，白人人群罹患ALS的风险更高。结论：本综述阐明了拉丁美洲地区ALS的异质性特征，并指出其与欧洲及北美地区存在特异性差异。但由于纳入研究在方法学层面存在异质性，本综述无法得出确定性结论。