Objective: Several studies have shown that glucocerebrosidase gene (GBA) mutations are strongly associated with the development of Lewy body diseases (LBD) and that idopathic REM sleep behavior disorder (IRBD) represents the prodromal state of them [1]. Thus, we wanted to find out whether GBA mutations are overrepresented in IRBD and if their frequency is similar to that reported for Parkinson’s disease (PD) and dementia with Lewy bodies (DLB).

Background: RBD is a condition characterized by nightmares and dream-enacting behaviors emerging in REM sleep. Patients with IRBD have no cognitive and no motor complains and epidemiological data indicate that IRBD mostly occurs in individuals older than 60 years. Different longitudinal studies demonstrated that most patients with an initial diagnosis of IRBD developed Lewy body diseases (LBD) with disease progression.

Methods: Mutational analysis of the GBA gene was carried out in a cohort of 69 patients with IRBD and 77 control individuals. IRBD diagnosis was reached according to the following criteria: (1) history of dream-enacting behaviors; (2) V-PSG showing REM sleep with increased electromyographic activity associated with abnormal behaviors; (3) absence of a neurodegenerative disease; (4) lack of motor and cognitive complaints, and (5) the clinical picture not better explained by another disorder, medication, or substance abuse [2]. Mutation search was carried out by Sanger sequencing of all GBA exons taking into account sequence similarity with the pseudogene GBAP1.

Results: One silent mutation (N392N) was identified in a control individual and 7 missense mutations in 8 IRBD patients. Of these, 4 had been described as LBD-related mutations, N370S, L444P, T369M, E326K; and three, R329C, A446T, and A318G, were found for the first time in this context. Whereas N370S and L444P are the most frequent GBA mutations present in PD, E326K shows a strong association with DLB and was detected in 2 IRBD patients. The frequency of 11.6% found in the present cohort was similar to that we reported recently for DLB (10.3%) and PD (16%) [3].

Conclusions: GBA mutations are accumulated in IRBD with a frequency similar to those found in DLB and PD underlining previous observations reporting IRBD as prodromal state of synucleinopathies.

References: 1. Boeve BF. Idiopathic REM sleep behavior disorder in the development of Parkinson’s disease. Lancet Neurol 2013;12:469–82.

2. Fernández-Arcos A, et al. The Clinical Phenotype of Idiopathic Rapid Eye Movement Sleep Behavior Disorder at Presentation: A Study in 203 Consecutive Patients. Sleep 2016;39:121-32.

3. Gámez-Valero A, et al. GBA Mutations Are Associated With Earlier Onset and Male Sex in Dementia With Lewy Bodies. Mov Disord 2016;31:1066-70.

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/glucocerebrosidase-mutations-in-idiopathic-rem-sleep-disorder/