Avner Thaler1, Noa Bregman2, Tanya Gurevich3, Tamara Shiner4, Yonatan Dror5, Ofir Zmira6, Ziv Gan-Or7, Anat Bar-Shira8, Mali Gana-Weisz8, Avi Orr-Urtreger9, Nir Giladi3, Anat Mirelman10. 1. Movement Disorders Unit, Neurological Institute, Tel-Aviv Medical Center, Israel; Sackler School of Medicine, Tel-Aviv University, Israel; Sagol School of Neuroscience, Tel-Aviv University, Israel. Electronic address: avnert@tlvmc.gov.il. 2. Memory and Attention Disorders Center, Neurological Institute, Tel-Aviv Medical Center, Israel. 3. Movement Disorders Unit, Neurological Institute, Tel-Aviv Medical Center, Israel; Sackler School of Medicine, Tel-Aviv University, Israel; Sagol School of Neuroscience, Tel-Aviv University, Israel. 4. Movement Disorders Unit, Neurological Institute, Tel-Aviv Medical Center, Israel; Sackler School of Medicine, Tel-Aviv University, Israel; Sagol School of Neuroscience, Tel-Aviv University, Israel; Memory and Attention Disorders Center, Neurological Institute, Tel-Aviv Medical Center, Israel. 5. Sackler School of Medicine, Tel-Aviv University, Israel. 6. Sheba Academic Medical Center Hospital, Israel. 7. Genetic Institute, Tel-Aviv Medical Center, Israel; Department of Neurology & Neurosurgery, McGill University, Canada; Montreal Neurological Institute, McGill University, Canada; Department of Human Genetics, McGill University, Montreal, QC, Canada. 8. Genetic Institute, Tel-Aviv Medical Center, Israel. 9. Sackler School of Medicine, Tel-Aviv University, Israel; Genetic Institute, Tel-Aviv Medical Center, Israel. 10. Sackler School of Medicine, Tel-Aviv University, Israel; Sagol School of Neuroscience, Tel-Aviv University, Israel; Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel.
Abstract
OBJECTIVE: Mutations in the glucocerebrosidase (GBA) gene are divided into mild and severe (mGBA, sGBA) based on their contribution to the phenotype of Gaucher disease (GD) among homozygotes. We conducted a longitudinal analysis of Parkinson's disease (PD) patients carrying mutations in the GBA gene to better characterize genotype-phenotype correlations. METHODS: Patients underwent a comprehensive assessment of medical, neurological, cognitive and non-motor functions. Data from these patients was explored to evaluate differences in disease phenotype based on genotype. RESULTS: A total of 355 PD patients participated in this study; 152 idiopathic PD patients, 139 mGBA, 48 sGBA and 16 GD-PD. Groups were similar in age, sex, years of education and age of onset. Both sGBA and GD-PD had higher Unified Parkinson Disease Rating Scale (UPDRS) scores (p = 0.041), higher frequencies of REM sleep behavior disorder (RBD) (p = 0.022) and hallucinations (p < 0.0001) compared to the other groups of patients. sGBA experienced more non-motor symptoms (p < 0.0001), depression (p < 0.001) and worse hyposmia (p = 0.010). Trail making test was significantly longer in GD-PD followed by sGBA, mGBA and iPD (p = 0.005). DISCUSSION: Motor, cognitive, olfactory and psychiatric symptoms are more severe in sGBA and GD-PD compared to mGBA and iPD, reinforcing the notion that the severity of the PD phenotype is related to the severity of the mutation in the GBA gene.
OBJECTIVE: Mutations in the glucocerebrosidase (GBA) gene are divided into mild and severe (mGBA, sGBA) based on their contribution to the phenotype of Gaucher disease (GD) among homozygotes. We conducted a longitudinal analysis of Parkinson's disease (PD) patients carrying mutations in the GBA gene to better characterize genotype-phenotype correlations. METHODS:Patients underwent a comprehensive assessment of medical, neurological, cognitive and non-motor functions. Data from these patients was explored to evaluate differences in disease phenotype based on genotype. RESULTS: A total of 355 PDpatients participated in this study; 152 idiopathic PDpatients, 139 mGBA, 48 sGBA and 16 GD-PD. Groups were similar in age, sex, years of education and age of onset. Both sGBA and GD-PD had higher Unified Parkinson Disease Rating Scale (UPDRS) scores (p = 0.041), higher frequencies of REM sleep behavior disorder (RBD) (p = 0.022) and hallucinations (p < 0.0001) compared to the other groups of patients. sGBA experienced more non-motor symptoms (p < 0.0001), depression (p < 0.001) and worse hyposmia (p = 0.010). Trail making test was significantly longer in GD-PD followed by sGBA, mGBA and iPD (p = 0.005). DISCUSSION: Motor, cognitive, olfactory and psychiatric symptoms are more severe in sGBA and GD-PD compared to mGBA and iPD, reinforcing the notion that the severity of the PD phenotype is related to the severity of the mutation in the GBA gene.
Authors: Reena V Kartha; James Joers; Marcia R Terluk; Abigail Travis; Kyle Rudser; Paul J Tuite; Neal J Weinreb; Jeanine R Jarnes; James C Cloyd; Gülin Öz Journal: J Inherit Metab Dis Date: 2019-12-17 Impact factor: 4.982