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Published on: July 16, 2021
Occurrence of Amyotrophic Lateral Sclerosis in Type 1 Gaucher Disease
Lais M Oliveira1, Tara Rastin1, Graeme A M Nimmo1
1Krembil Research Institute (L.M.O., L.V.K.), Toronto Western Hospital, University Health Network, Ontario; Djavad Mowafaghian Centre for Brain Health (T.R.), Division of Neurology, Department of Medicine, University of British Columbia, Vancouver; Mark Feedman and Judy Jacobs Program for Gaucher Disease (G.A.M.N., D. Amato, L.V.K.), Mount Sinai Hospital; Fred A. Litwin Family Centre for Genetic Medicine (G.A.M.N., D.-L.N.), Department of Medicine, Mount Sinai Hospital and Toronto General Hospital, University Health Network, University of Toronto, Ontario; Department of Human Genetics (J.P.R., P.A.D., G.A.R., Z.G.-O.), Montreal Neurological Institute and Hospital (J.P.R., P.A.D., G.A.R., Z.G.-O.), and Department of Neurology and Neurosurgery (P.A.D., G.A.R., Z.G.-O.), McGill University, Quebec; Tanz Centre for Research in Neurodegenerative Diseases (M.Z., E.A.R., L.V.K.), University of Toronto, Ontario, Canada; Shanghai First Rehabilitation Hospital (M.Z.), School of Medicine, Clinical Center for Brain and Spinal Cord Research (M.Z.), and Institute for Advanced Study (M.Z.), Tongji University, Shanghai, China; Department of Neurology (D. Arkadir, M.G.), Hadassah Medical Center, Hebrew University, Jerusalem, Israel; Ellen and Martin Prosserman Centre for Neuromuscular Diseases (C.B.), Division of Neurology, Department of Medicine, Toronto General Hospital, University Health Network, University of Toronto; London Health Sciences Centre (C.L.S.), London, Ontario, Canada; Gaucher Unit (A.Z.), Shaare Zedek Medical Center, Hadassah Medical School, Hebrew University, Jerusalem, Israel; Division of Neurology (L.Z.), Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto; and Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (L.V.K.), Division of Neurology, Department of Medicine, Toronto Western Hospital, University Health Network, University of Toronto, Ontario, Canada.
Objective:
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.
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 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.
Results:
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.
Conclusions:
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.
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