Objective: To assess the role of glycosphingolipids in increased risk of Parkinson’s disease (PD) in patients with Gaucher disease (GD).

Background: Patients with GD are at increased risk of PD. Controversy exists regarding the biochemical pathways linking the two diseases. It remains unclear whether neuronal death is secondary to increased levels of glycosphingolipids or to accumulation of the misfolded glucocerebrosidase. Glucosylsphingosine (Lyso-Gb1), a sensitive and specific biomarker for GD, can help resolve this issue.

Methods: We tested Lyso-Gb1 serum levels (Centogene, Rostock, Germany) in GD patients with PD and compared the result of each patient with a mutation-matched control group. Participants were not on enzyme-replacement therapy. To normalize the distribution of Lyso-Gb1 values they were log-transformed and then z-scored.   

Results: Lyso-Gb1 levels were tested in four GD-PD patients with a N370S mutation in the GBA gene and an additional in-trans mutation (N370S, L444P, V394L or RecTL). Lyso-Gb1 values were lower in all GD-PD individuals when compared with their relevant control group (z-scores: -0.55,  -1.53, -3.47, -3.75, respectively to in-trans mutation).

Conclusions: The hypothesis that high levels of glycosphingolipids are a major cause of increased risk of PD in GD patients is not supported by our results.  

References: Rolfs, A. et al. Glucosylsphingosine Is a Highly Sensitive and Specific Biomarker for Primary Diagnostic and Follow-Up Monitoring in Gaucher Disease in a Non-Jewish, Caucasian Cohort of Gaucher Disease Patients. PLoS ONE 8, e79732 (2013).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-disease-in-untreated-gaucher-patients-is-associated-with-reduced-glucosylsphingosine-lyso-gb1-serum-levels/