Genetic Studies of Lysosomal Storage Disorders
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|ClinicalTrials.gov Identifier: NCT00001215|
Recruitment Status : Enrolling by invitation
First Posted : November 4, 1999
Last Update Posted : June 24, 2022
The purpose of this study is to identify genetic, biochemical, and clinical factors that are associated with disease severity in people with Gaucher disease and other lysosomal storage disorders.
There is a vast spectrum of clinical manifestations in people with Gaucher disease as well as other lysosomal storage disorders. This study will evaluate patients with lysosomal disorders on an outpatient or inpatient basis in order to better characterize the clinical, genetic, and pathophysiological features of these disorders. Participants will be re-evaluated on an annual basis.
|Condition or disease|
|Lysosomal Storage Disorders Gaucher Disease Parkinson Disease|
There is a vast spectrum of clinical manifestations encountered in individuals with lysosomal storage diseases. Lysosomal storage disorders occur when an enzyme necessary for breaking down intracellular fats, proteins, recycled products and organelles in the cell is deficient. As a result, substrate accumulates within the lysosomes affecting different organ systems. The most common lysosomal storage disease, Gaucher disease (GD), results from the inherited deficiency of the enzyme glucocerebrosidase, which breaks down the lipid glucocerebroside. The disease is characterized by extremely variable manifestations, with some patients presenting in childhood with hepatosplenomegaly, anemia, thrombocytopenia and bony problems, some in infancy with a lethal neurodegeneriative course, while others remain asymptomatic into their eighth decade. GD has traditionally been divided into three clinical subtypes, type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (chronic neuronopathic) delineated by the absence or presence of neurologic involvement and its rate of progression. Some patients, however, defy classification into these three categories, and it may be more accurate to regard GD as a continuum of phenotypes. In addition, patients and carriers of mutations in GBA1, the gene for GD, are at increased risk for developing Parkinson disease (PD) and related neurodegenerative disorders.
This is a longitudinal natural history study of patients with lysosomal storage disorders with emphasis on phenotypic heterogeneity of GD and those at risk for the development of parkinsonism. Our goal is to identify genetic, biochemical, and clinical parameters that are associated with disease severity in individuals with lysosomal storage disorders to identify individuals with milder or early phenotypic manifestations, and to explore the natural history and extent of associated clinical manifestations. We also study subjects with GBA1 mutations who are at higher risk for developing parkinsonism to identify early disease manifestations and potential biomarkers. Participants are evaluated at the NIH to better characterize the clinical, genetic and pathophysiological features of these disorders. In order to better understand the entire effect of the enzyme deficiencies and the function of the specific proteins involved, emphasis is placed on individuals with atypical presentations. In particular, we will focus on subjects with GD and PD, to better understand the association between the two disorders. Following an initial comprehensive workup, participants will be studied either in the inpatient wards or the outpatient clinic, and will be re-evaluated at periodic intervals longitudinally.
|Study Type :||Observational|
|Estimated Enrollment :||1050 participants|
|Official Title:||Studies of Genetic Heterogeneity in Patients With Lysosomal Storage Disorders|
|Actual Study Start Date :||May 16, 1986|
a family member of a documented proband
the participant on initial screening must be found to have or be a carrier of a documented lysosomal storage disorder
- Clinical Phenotypes [ Time Frame: ongoing ]The purpose of this study is to clearly describe the clinical phenotypes of individuals with lysosomal storage diseases in order to better understand the pathophysiology of these disorders and to develop new therapies.
- development of Parkinsonism [ Time Frame: ongoing ]We aim to identify factors that may be predictive of the development of Parkinsonism in an at-risk population
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001215
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Ellen Sidransky, M.D.||National Human Genome Research Institute (NHGRI)|