Occurrence of Amyotrophic Lateral Sclerosis in Type 1 Gaucher Disease

Abstract

ObjectiveTo 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.MethodsWe 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.ResultsWe 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.ConclusionsThe 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.

Frequency of Parkinson’s Disease Genes and Role of PARK2 in Amyotrophic Lateral Sclerosis: An NGS Study

“…Interestingly, pathogenic variants in GBA have also been found in FTD [ 31 ], and ALS patients show in the latter a more compromised cognitive profile [ 16 ]. Our results are in line with previous studies [ 16 , 43 ], confirming that the frequency of GBA variants in the ALS cohort is similar to that of European population controls in the gnomAD database.…”

Genetic Testing in Clinical Movement Disorders: A Case-Based Review

“…There are suggestions that GBA1 may be associated with multiple system atrophy, 12 13 14 and we have also raised the possibility of an association between GBA1 and amyotrophic lateral sclerosis. 15 Further, rare cases of a progressive supranuclear palsy (PSP)-type presentation have been reported with LRRK2 . 16 17 Thus, the significance of atypical parkinsonism or other neurodegenerative diseases in a patient's pedigree should be considered.…”

Rapid-Onset Dystonia and Parkinsonism in a Patient With Gaucher Disease

“…Similar to sporadic PD, neuropathological features include the degeneration of dopaminergic neurons and α-synuclein-containing Lewy bodies [ 10 ]. In addition, atypical neurological phenotypes have been described in GBA1 mutation carriers, including multiple system atrophy (MSA) [ 11 ] corticobasal syndrome (CBS) [ 12 ] and amyotrophic lateral sclerosis (ALS) [ 13 ]. However, the association between GBA1 mutations and these other movement disorders is still uncertain.…”