Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Genetics
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To assess the phenotype of Parkinson’s disease (PD) patients in homozygote or compound heterozygote carriers of mutations in the β-glucocerebrosidase gene (GBA).
Background: Gaucher’s disease (GD), an autosomal recessive disorder is characterized by easy bruising, fatigue, anemia, thrombocytopenia and hepatosplenomegaly. GBA has been implicated in PD susceptibility with heterozygote carriers of severe GBA mutations experiencing a 10-fold increase risk for the development of PD. While the heterozygote phenotype of GBA has been widely reported, clinical studies that characterize the PD phenotype in GD patients are lacking.
Methods: This cross sectional study assessed motor, cognitive, olfactory and autonomic functions in a cohort of Ashkenazi Jewish PD patients. Genetic screening for nine common mutations in the GBA gene was performed. Demographic data and medical history was collected and compared with age and disease duration matched idiopathic PD patients. Participants were evaluated using the Unified Parkinson’s disease Rating Scale (UPDRS), Montreal Cognitive Assessment test (MoCA), Trail Making Test (TMT), Digit Span, Verbal Fluency, Stroop, the University of Pennsylvania Smell Identification Test (UPSIT), Scales of Outcome in PD – Autonomic (SCOPA-AUT), Geriatric Depression Scale (GDS), Non-Motor Symptom Questionnaire (NMS) and REM sleep behavior disorder questionnaire (RBDQ).
Results: From a total of 1050 Ashkenazi Jewish PD patients that were screened, 12 were found to be either homozygote or compound heterozygote for mutations in the GBA gene. GD-PD patients were found to have more severe UPDRS part III scores (28.64±10.06, vs 18.58±6.89), lower MoCA scores (23.09±3.21 vs 26.58±2.53), lower UPSIT scores (11.40±6.35 vs 19.30±6.66), have higher prevalence of RBD (33% vs 16.6%) and higher frequencies of hallucinations (50% vs. 13%) compared to idiopathic PD patients
| Mutation | Gender | Age | Age of Onset | Disease Duration | UPDRS III | MoCA | |
| P1 | N370S/N370S | F | 52 | 41 | 11 | 37 | 20 |
| P2 | N370S/N370S | F | 56 | 47 | 9 | 23 | 21 |
| P3 | N370S/V394L | M | 56 | 43 | 13 | 31 | 25 |
| P4 | RecTL/N370S | M | 62 | 52 | 10 | 43 | 16 |
| P5 | RecTL/N370S | M | 57 | 44 | 13 | 35 | 12 |
| P6 | N370S/R496H | F | 40 | 39 | 1 | 25 | 24 |
| P7 | IVS2+1/N370S | M | 61 | 52 | 9 | 16 | 22 |
| P8 | RecTL/N370S | F | 78 | 72 | 6 | 29 | 25 |
| P9 | N370S/N370S | M | 73 | 65 | 8 | 35 | 28 |
| P10 | N370S/V394L | M | 66 | 66 | 1 | 15 | 29 |
| P11 | N370S/R496H | M | 47 | 45 | 2 | 17 | 28 |
| P12 | N370S/L444P | M | 53 | 51 | 3 | 40 | 24 |
| Mean±SD | 66% M | 58.41±10.56 | 51.41±10.47 | 13.16±7.15 | 28.83±9.61 | 23.09±5.2 |
Conclusions: PD patients who are homozygote or compound heterozygote for mutations in the GBA gene have a more severe disease phenotype in all domains assessed herein apart from mood and autonomic functions compared to age and disease matched idiopathic PD patients.
Israeli Annual Neurological Conference 2015.
To cite this abstract in AMA style:
A. Thaler, A. Mirelman, E. Shimoni, M. Victor, O. Assais, M. Grumberg, T. Gurevich, T. Shiner, M. Gana Weisz, A. Orr Urtreger, N. Giladi. Parkinson’s disease characteristics in patients with Gaucher’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/parkinsons-disease-characteristics-in-patients-with-gauchers-disease/. Accessed May 9, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-disease-characteristics-in-patients-with-gauchers-disease/