Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders
National Human Genome Research Institute (NHGRI)
Summary
Study description: This is a natural history study that will evaluate any patient with enzyme or DNA confirmed GM1 or GM2 gangliosidosis, sialidosis or galactosialidosis. Patients may be evaluated every 6 months for infantile onset disease, yearly for juvenile onset and approximately every two years for adult-onset disease as long as they are clinically stable to travel. Data will be evaluated serially for each patient, and cross-sectionally for patients of similar ages and genotypes. Genotype-phenotype correlations will be made where possible although these are rare disorders and the majority of the patients are compound heterozygotes. Objectives: To study the natural history and progression of neurodegeneration in individuals with glycosphingolipid storage disorders (GSL), GM1 and GM2 gangliosidosis, and glycoprotein (GP) disorders including sialidosis and galactosialidosis using clinical evaluation of patients and patient/parent surveys. To develop sensitive tools for monitoring disease progression. To identify biological markers in blood, cerebrospinal fluid, and urine that correlate with disease severity and progression and can be used as outcome measures for future clinical trials. To further understand and characterize the mechanisms of neurodegeneration in GSL and GP storage disorders across the spectrum of disease beginning with ganglioside storage in fetal life. Endpoints: Exploring the natural history of Lysosomal Storage Diseases and Glycoprotein Disorders Study Population: Patients with enzyme or DNA confirmed GM1 or GM2 gangliosidosis, sialidosis or galactosialidosis. Accrual ceiling is 200 participants. No exclusions based on age, gender, demographic group, or demographic location. Patients included in our study are those that are seen at the NIH Clinical Center, subjects that have only sent in blood samples, as well as those who complete the questionnaire or provided head circumference measures.
Description
The GM1 and GM2 gangliosidoses are rare lysosomal storage disorders that primarily affect the brain and are uniformly fatal. The glycoproteinoses sialidosis and galactosialidosis are ultra-rare disorders involving predominantly the skeletal and central nervous systems that are likewise fatal or severely debilitating. No effective therapy for patients with these diseases has yet been demonstrated. Historically, since these disorders are fatal very little natural history information or disease characterization using modern medical techniques has been collected. This information is vital to estab…
Eligibility
- Age range
- 0–100 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: Any individual with GM1 or GM2 gangliosidosis, sialidosis or galactosialidosis documented by enzyme deficiency or mutation analysis in a CLIA-approved laboratory will be eligible for the study. EXCLUSION CRITERIA: There will be no exclusion based on race, gender, or ethnicity; however particular ethnic groups may be overrepresented due to the frequency of the diseases in a specific population (e.g., Ashkenazi Jews in infantile and adult GM2 and Roma "travelers" in juvenile GM1). The majority of juvenile subjects will have severely impaired decision-making and even info…
Location
- National Institutes of Health Clinical CenterBethesda, Maryland