Evaluation of the frequency of non-motor symptoms of Parkinson\u2019s disease in adult patients with Gaucher disease type 1

Matheus V M B Wilke,Suelen P Basgalupp,Marina Siebert,Ida V D Schwartz,Otavio B Piltcher,Alícia D Dornelles,Tatiele Nalin,Artur S Schuh,Filippo P Vairo

doi:10.1186/s13023-019-1079-4

Abstract

BackgroundGaucher disease (GD) is caused by deficiency of beta-glucocerebrosidase (GCase) due to biallelic variations in the GBA1 gene. Parkinson’s disease (PD) is the second most common neurodegenerative condition. The classic motor symptoms of PD may be preceded by many non-motor symptoms (NMS), which include hyposmia, rapid eye movement (REM) sleep behavior disorder, constipation, cognitive impairment, and depression. Population studies have identified mutations in GBA1 as the main risk factor for idiopathic PD. The present study sought to evaluate the prevalence of NMS in a cohort of patients with GD type 1 from Southern Brazil.MethodologyThis is an observational, cross-sectional study, with a convenience sampling strategy. Cognition was evaluated by the Montreal Cognitive assessment (MoCa), daytime sleepiness by the Epworth Scale, depression by the Beck Inventory, constipation by the Unified Multiple System Atrophy Rating Scale, and REM sleep behavior disorder by the Single-Question Screen; hyposmia by the Sniffin’ Sticks. Motor symptoms were assessed with part III of the Unified Parkinson’s Disease Rating Scale. All patients were also genotyped for the GBA1 3′-UTR SNP (rs708606).ResultsTwenty-three patients (female = 13; on enzyme replacement therapy = 21, substrate reduction therapy = 2) with a mean age of 41.45 ± 15.3 years (range, 22–67) were included. Eight patients were found to be heterozygous for the 3′-UTR SNP (rs708606). Fourteen patients (8 over age 40 years) presented at least one NMS; daytime sleepiness was the most frequent (n = 10). Two patients (aged 63 and 64, respectively) also presented motor symptoms, probably drug-related.ConclusionsNMS were prevalent in this cohort. We highlight the importance of a multidisciplinary follow-up focusing on earlier diagnosis of PD, especially for patients with GD type 1 over the age of 40.

Highlights

Gaucher disease (GD, OMIM 230800) is caused by deficient activity of beta-glucocerebrosidase (GCase) due to biallelic pathogenic variants in the GBA1 gene located at chromosome 1q21
We highlight the importance of a multidisciplinary follow-up focusing on earlier diagnosis of Parkinson’s disease (PD), especially for patients with GD type 1 over the age of 40
Carriers for mutations in GBA1 and patients with GD have a lifetime relative risk of developing PD greater than that of the overall population, which depends on the age and on the the mutations [9,10,11,12]

Summary

Introduction

Gaucher disease (GD, OMIM 230800) is caused by deficient activity of beta-glucocerebrosidase (GCase) due to biallelic pathogenic variants in the GBA1 gene located at chromosome 1q21. GD is one of the most common lysosomal disorders, with an estimated worldwide incidence of 1 case per 57,000 live births [1, 2]. The motor symptoms of PD are preceded by a prodromal period of up to 20 years. The so-called non-motor symptoms (NMS) that occur during this prodrome, such as hyposmia, rapid eye movement (REM). Population studies have identified GBA1 mutations as the main risk factor for idiopathic PD (iPD). A small cohort study suggested that mutations in exonic regions and a single nucleotide polymorphism (SNP) in the 3′-UTR of GBA1 (rs708606) in the intron-exon boundaries is implicated in the cognitive symptoms of PD [13]

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