Follow-up of pre-motor symptoms of Parkinson’s disease in adult patients with Gaucher disease type 1 and analysis of their lysosomal enzyme profiles in the CSF

Orphanet Journal of Rare Diseases

Research

Dévora Natalia Randon¹  Roberto Giugliani²  Francyne Kubaski³  Gabrielle Dineck Iop⁴  Layzon Antonio da Silva⁴  Larissa Faqueti⁴  Fernanda Bender Pasetto⁵  Fernanda Medeiros Sebastião⁵  Kristiane Michelin Tirelli⁵  Franciele Fátima Lopes⁵  Fabiano Poswar⁶  Ida Vanessa Doederlein Schwartz⁷  Matheus Vernet Machado Bressan Wilke⁸  Artur Francisco Schumacher Schuh⁹  Wyllians Vendramini Borelli^1,10 

[1] BRAIN Laboratory, HCPA, Porto Alegre, RS, Brazil;BRAIN Laboratory, HCPA, Porto Alegre, RS, Brazil;Biodiscovery Laboratory, HCPA, Porto Alegre, RS, Brazil;Department of Genetics, UFRGS, Porto Alegre, RS, Brazil;Biochemical Genetics Laboratory, Greenwood Genetics Center, Greenwood, SC, USA;Biodiscovery Laboratory, HCPA, Porto Alegre, RS, Brazil;LEIM- Genetics Laboratory - Serviço de Genética Médica, Medical Genetics Service, HCPA, Porto Alegre, RS, Brazil;Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos St., 2350, 3Rd Floor, 90035-007, Porto Alegre, RS, Brazil;Postgraduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre, RS, Brazil;Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos St., 2350, 3Rd Floor, 90035-007, Porto Alegre, RS, Brazil;Postgraduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre, RS, Brazil;BRAIN Laboratory, HCPA, Porto Alegre, RS, Brazil;Department of Genetics, UFRGS, Porto Alegre, RS, Brazil;Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos St., 2350, 3Rd Floor, 90035-007, Porto Alegre, RS, Brazil;Postgraduate Program in Medical Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil;Neurology Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil;Department of Pharmacology, UFRGS, Porto Alegre, RS, Brazil;Neurology Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil;Pharmacology and Therapeutics research program, UFRGS, Porto Alegre, Brazil;

关键词: Gaucher disease;    Parkinson`s disease;    Non-motor symptoms;    Cerebrospinal fluid;   

DOI  :  10.1186/s13023-023-02875-3

 received in 2023-05-26, accepted in 2023-08-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. Its classic motor symptoms may be preceded by non-motor symptoms (NMS). Population studies have identified GBA variants as risk factors for idiopathic PD. The increased risk of PD has also been suggested in other Lysosomal Storage Disorders (LSDs). Objective: To assess the evolution of the prevalence of NMS compatible with PD in a cohort of South Brazilian adult patients with Gaucher Disease (GD) type 1, already evaluated 3 years ago (2018). Cerebrospinal Fluid (CSF) was collected to assess the levels of LSD enzymes (beta-hexosaminidases, beta-glucuronidase) and biomarker of macrophage activation (chitotriosidase, ChT), compared to controls (metachromatic leukodystrophy, MLD). Cognition was evaluated by the Montreal Cognitive Assessment (MoCA) questionnaire, daytime sleepiness by the Epworth Sleepiness Scale (ESS), depression by Beck´s Inventory, constipation by the Unified Multiple System Atrophy Rating Scale (UMSARS) scale, and REM sleep behavior disorder by the single-question screen. Hyposmia was assessed with Sniffin’ Sticks (SST).ResultsNineteen patients completed the follow-up (mean age of the sample was 44 years; range, 26–71). The patient with the highest number of NMS at the baseline (4 including the lowest SST score) was diagnosed with PD four years later. Apart from an improvement in the ESS score, no other statistical significance was found between the number of NMS between the first and second evaluation, nor between patients with one L444P variant (n = 5) and the rest of the cohort. CSF was collected in five patients (mean age of the sample was 40 years, range 30–53. A significant difference was found in the mean CSF activity levels of beta-hexosaminidases and beta-glucuronidase between GD1 and MLD patients. Mean ChT (CSF) was 62 nmol/h/mL in GD patients and 142 in MLD (n = 6) patients.ConclusionsThe patient with the highest number of NMS in our 2018 cohort was the one that developed PD, corroborating with the importance of this longitudinal follow-up. CSF and plasma analysis might allow a better understanding of the neurodegenerative processes connecting PD and the lysosomal environment. Further analysis is needed to understand this relationship.

【 授权许可】

CC BY   
© Institut National de la Santé et de la Recherche Médicale (INSERM) 2023

【 图 表 】

Fig. 4