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. 2023 Oct 2;18(1):309.
doi: 10.1186/s13023-023-02875-3.

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

Matheus Vernet Machado Bressan Wilke  1   2 , Fabiano Poswar  1   3 , Wyllians Vendramini Borelli  4   5 , Kristiane Michelin Tirelli  6 , Dévora Natalia Randon  7 , Franciele Fátima Lopes  6 , Fernanda Bender Pasetto  6 , Fernanda Medeiros Sebastião  6 , Gabrielle Dineck Iop  8 , Larissa Faqueti  8 , Layzon Antonio da Silva  8 , Francyne Kubaski  9 , Artur Francisco Schumacher Schuh  4   10 , Roberto Giugliani  7   8   11 , Ida Vanessa Doederlein Schwartz  12   13   14   15
Affiliations

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

Matheus Vernet Machado Bressan Wilke et al. Orphanet J Rare Dis. .

Abstract

Background: Parkinson'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).

Results: Nineteen 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.

Conclusions: The 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.

Keywords: Cerebrospinal fluid; Gaucher disease; Non-motor symptoms; Parkinson`s disease.

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Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Flow diagram of patient enrollment
Fig. 2
Fig. 2
Lysosomal enzymes activity in the cerebrospinal fluid of patients with Gaucher Disease type 1 (GD1, n=5) and Metachromatic leukodystrophy (MLD, n=6)
See this image and copyright information in PMC

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