Study to Determine Mutations in the Gaucher Gene in Patients With Idiopathic Parkinson's Disease for Phenotype-genotype Correlation

Completed

• Conditions: Idiopathic Parkinson Disease; Parkinson Disease

• Registration Number: NCT01272687
• Lead Sponsor: CENTOGENE GmbH Rostock

Brief Summary

The genotype-phenotype correlation in patients with Parkinson's disease with specific mutations in the glucocerebrosidase gene (Gaucher gene) is known from own clinical experiences as well as from case reports in the literature. The epidemiological study will determine the frequency of heterozygous mutations in the glucocerebrosidase gene and correlate to the clinical onset and development by measuring and documenting severity of symptoms (e.g. cognitive deficits, L-dopa responsiveness, depression) in clinically well-characterized Parkinson's patients.

Detailed Description

Parkinson's disease (also known as Parkinson's, Parkinson disease, or PD) is a degenerative disorder of the central nervous system that impairs motor skills, cognitive processes, and other functions. The most obvious symptoms are motor-related, including tremor, rigidity, slowness of movement, and postural instability. Among non-motor symptoms are autonomic dysfunction and sensory and sleep difficulties. Cognitive and neurobehavioral problems, including dementia, are common in the advanced stages of the disease. PD usually appears around the age of 60, although there are young-onset cases.

Gaucher's disease is a genetic disease in which a fatty substance (lipid) accumulates in cells and certain organs. Gaucher's disease is the most common of the lysosomal storage diseases. It is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as acid β-glucosidase). The enzyme acts on a fatty substance glucocerebroside (also known as glucosylceramide). When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells (mononuclear leukocytes). Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain and bone marrow.

Symptoms of Parkinson's syndrome in classical type 1 Gaucher patients were first systematically described in 1996. In GD patients, a marked heterogeneity is detected in terms of disease-causing mutations. In 17 Gaucher patients with symptoms of Parkinson's disease, 12 different genotypes were sequenced and compared to other Parkinson's patients, a lower L-dopa responsiveness, a higher frequency of cortical dysfunction and a relatively early onset of the symptoms was described. Many of these Gaucher patients with clinical Parkinson's symptoms had a positive family history of Parkinson's disease among relatives with heterozygous mutations in the Gaucher gene that could be confirmed in systematic studies.

Study Timeline

• Study Start: 2011-01
• Study First Submitted: 2011-01-07
• Study First Submitted QC: 2011-01-07
• Study First Posted: 2011-01-10
• Primary Completion: 2016-06
• Study Completion: 2017-06
• Status Verified: 2020-04
• Last Update Submitted: 2021-04-08
• Last Update Posted: 2021-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1500

Inclusion Criteria

• Male or female patients at 18 years old
• Patients with confirmed diagnosis of Parkinson's disease
• Signed informed consent

Exclusion Criteria

• Male or female patients being younger than 18 years old
• Patients without confirmed diagnosis of Parkinson's disease
• Missing signed informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Trial Locations

Locations (15)

Gertrudis-Kliniken im Parkinson-Zentrum; 🇩🇪 Leun, Germany

Stiftung Deutsche Klinik für Diagnostik GmbH Fachbereich Neurologie; 🇩🇪 Wiesbaden, Germany

Fachkrankenhaus für neurologische Akut- und Rehabilitationsmedizin; 🇩🇪 Bad Neustadt An Der Saale, Germany

Universitätsklinikum Dresden Klinik für Neurologie; 🇩🇪 Dresden, Germany

Universitätskrankenhaus Hamburg-Eppendorf, Department of Neurology; 🇩🇪 Hamburg, Germany

HANSE-Klinikum, Department of Neurology; 🇩🇪 Stralsund, Germany

Alexianer Krefeld GmbH, Krankenhaus Maria Hilf; 🇩🇪 Krefeld, Germany

University of Ulm, Department of Neurology; 🇩🇪 Ulm, Germany

University of Giessen, Department of Neurology; 🇩🇪 Giessen, Germany

Ernst-Moritz-Arndt-University of Greifswald, Department of Neurology; 🇩🇪 Greifswald, Germany

Neurologischische Arztpraxis; 🇩🇪 Rostock, Germany

Universitätsklinikum Rostock, Klinik für Neurologie; 🇩🇪 Rostock, Germany

Klinikverbund Südwest, Klinikum Sindelfingen-Böblingen; 🇩🇪 Sindelfingen, Germany

Chulalongkorn University Hospital; 🇹🇭 Bangkok, Thailand

Medizinische Hochschule Hannover, Bewegungsstörungsambulanz; 🇩🇪 Hannover, Germany