To report the association between type 1 Gaucher disease (GD1) and amyotrophic lateral sclerosis (ALS) in 3 unrelated families and to explore whether GBA variants influence the risk of ALS.

We conducted retrospective chart reviews of patients with GD1 or their family members diagnosed with ALS. To further investigate whether there is an association between ALS and GD, we performed exploratory analyses for the presence of GBA variants in 3 ALS cohorts from Toronto (Canada), Montreal (Canada), and Project MinE (international), totaling 4,653 patients with ALS and 1,832 controls.

We describe 2 patients with GD1 and 1 obligate GBA mutation carrier (mother of GD1 patient) with ALS. We identified 0 and 8 GBA carriers in the Toronto and Montreal cohorts, respectively. The frequencies of GBA variants in patients with ALS in the Montreal and Project MinE cohorts were similar to those of Project MinE controls or Genome Aggregation Database population controls.

The occurrence of ALS in biallelic or monoallelic GBA mutation carriers described here, in addition to common pathogenic pathways shared by GD1 and ALS, suggests that GBA variants could influence ALS risk. However, analyses of GBA variants in ALS cohorts did not reveal a meaningful association. Examination of larger cohorts and neuropathologic studies will be required to elucidate whether patients with GD1 are indeed at increased risk for ALS.

报告3个无关家庭中的1型Gaucher病（GD1）与肌萎缩性侧索硬化症（ALS）之间的关联，并探讨GBA变体是否影响ALS的风险。

我们对GD1患者或其诊断为ALS的家庭成员进行了回顾性图表审查。为了进一步研究ALS与GD之间是否存在关联，我们对3个来自多伦多（加拿大），蒙特利尔（加拿大）和Project MinE（国际）的ALS队列中的GBA变异进行了探索性分析，共计4,653例ALS患者和1,832个控件。

我们描述了2例GD1患者和1例专性GBA突变携带者（GD1患者的母亲）患有ALS。我们分别在多伦多和蒙特利尔的队列中确定了0和8个GBA航空母舰。蒙特利尔和MinE项目组的ALS患者中GBA变异的频率与Project MinE对照或基因组聚合数据库人群对照的频率相似。

除了GD1和ALS共有的常见致病途径外，此处描述的双等位基因或单等位基因GBA突变携带者中ALS的发生，表明GBA变体可能影响ALS风险。但是，对ALS队列中的GBA变体进行分析并没有发现有意义的关联。将需要检查更大的队列和神经病理学研究，以阐明GD1患者是否确实确实患ALS的风险增加。