Objective: The objective of this study is to compare clinical features of early stage of Parkinson’s disease (PD) between with and without positive glucocerebrosidase (GBA) mutation.

Background: GBA mutation is known to be an important risk factor for PD [1]. PD patients with GBA mutations shows more rapid progression and prone to cognitive decline [2] [3]. On the other hand, clinical differences due to the presence or absence of GBA mutation in the early stage have not been fully investigated.

Method: GBA mutation was investigated in 104 patients with PD. For positive GBA mutation patients, age and gender matched pairs with negative GBA mutation patients were created. Clinical features were compared between two groups.

Results: Thirteen PD patients had positive pathological GBA mutation. Of those, two cases could not obtain patients without GBA mutation that fulfilled the conditions for matched pairs. Hence, eleven matched pairs were created. Age of onset, simple cognitive function tests, uptake of 123I-Meta-iodobenzylguanidine myocardial scintigraphy, olfactory discrimination ability did not differ between positive GBA mutation group and negative group. Positive GBA mutation group had more severe motor symptoms than negative group (mean score of Unified Parkinson’s Disease Rating Scale part 3 was 26.6 in positive and 17.9 in negative GBA mutation, p=0.033). Whereas the decrease in uptake of dopamine transporter scintigraphy on the dominantly affected side showed a tendency to be slighter in positive GBA mutation group (specific binding ratio 4.53 in positive and 3.24 in negative GBA mutation, p = 0.055). In the positive GBA mutation group, except for one patient, the initial symptom was not tremor.

Conclusion: This study showed that patients with Parkinson’s disease with GBA mutation had more severe motor symptoms in early stage. Though tremor is uncommon as initial manifestation in the positive GBA mutation PD patient, it is difficult to differentiate from negative mutation PD by usual clinical practice such as clinical findings and diagnostic images. Based on confirmation by genetic testing, optimized therapeutic approach for each disease condition was considered to be necessary.

References: 1. Sidransky E, Nalls MA, Aasly JO et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease. N Engl J Med. 2009 Oct 22;361(17):1651-61. 2. Brockmann K, Srulijes K, Pflederer S et al. GBA-associated Parkinson’s disease: reduced survival and more rapid progression in a prospective longitudinal study. Mov Disord. 2015 Mar;30(3):407-11. 3. Cilia R, Tunesi S, Marotta G et al. Survival and dementia in GBA-associated Parkinson’s disease: The mutation matters. Ann Neurol. 2016 Nov;80(5):662-673.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-stage-parkinsons-disease-patients-with-gba-mutation-have-more-severe-motor-symptoms-and-difficult-to-differentiate-in-routine-clinical-practice/