Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders

Conditions
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Myoclonus, Neurological Regression, Cherry Red Spot, Brain Atrophy

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Individuals greater than 6 months of age with GM1 or GM2 gangliosidosis documented by enzyme deficiency and/or mutation analysis in a CLIA-approved laboratory EXCLUSION CRITERIA: Individuals who in the opinion of the principal investigator are too medically fragile to travel safely to the NIH for evaluation Individuals unable to comply with the protocol
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Glycoprotein Disorders<br>Glycoprotein Disorders | |
| Lysosomal Storage Diseases<br>Lysosomal Storage Diseases | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exploring the natural history of Glycoprotein Disorders | Exploring the natural history of Glycoprotein Disorders | Assessed one to every two years | 
| Natural history of Lysosomal Storage Diseases | Exploring the natural history of Lysosomal Storage Diseases | Assessed one to every two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sialidosis, Lysosomal Storage, GM1 Gangliosidosis, GM2 Gangliosidosis, Natural History, Glycoprotein Disorders, Lysosomal Storage Disorder, Tay-Sachs, Sandhoff, Gaucher