Occurrence of Amyotrophic Lateral Sclerosis in Type 1 Gaucher Disease.

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

Methods: 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 variants in 3 ALS cohorts from Toronto (Canada), Montreal (Canada), and Project MinE (international), totaling 4,653 patients with ALS and 1,832 controls.

Results: We describe 2 patients with GD1 and 1 obligate mutation carrier (mother of GD1 patient) with ALS. We identified 0 and 8 carriers in the Toronto and Montreal cohorts, respectively. The frequencies of 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.

Conclusions: The occurrence of ALS in biallelic or monoallelic mutation carriers described here, in addition to common pathogenic pathways shared by GD1 and ALS, suggests that variants could influence ALS risk. However, analyses of 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.