Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders

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.

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Study Overview

• Status: Recruiting
• Conditions: Myoclonus; Neurological Regression; Cherry Red Spot; Brain Atrophy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Jean M Johnston; Phone Number: (240) 515-1448; Email: johnstonjm@mail.nih.gov
• Study Contact Backup: Name: Cynthia J Tifft, M.D.; Phone Number: (301) 451-8485; Email: cynthiat@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with Lysosomal Storage Diseases and Glycoprotein Disorders.

Description

• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Glycoprotein Disorders
Lysosomal Storage Diseases

What is the study measuring?

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ophthalmology assessments	Evaluating change over time in eye findings.	Every 6-24 months; depending on age of subject
Audiology testing	Evaluating change over time in auditory testing	Every 6-24 months; depending on age of subject
Laboratory testing	Evaluating disease biomarkers over time.	Every 6-24 months; depending on age of subject
Neurology assessments	Neurology assessments are done to measure change over time.	Every 6-24 months; depending on age of subject

Collaborators and Investigators

• Sponsor: National Human Genome Research Institute (NHGRI)
• Investigators: Principal Investigator: Cynthia J Tifft, M.D., National Human Genome Research Institute (NHGRI)

Publications and helpful links

General Publications

• Wada R, Tifft CJ, Proia RL. Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation. Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10954-9. doi: 10.1073/pnas.97.20.10954.
• Cantor RM, Roy C, Lim JS, Kaback MM. Sandhoff disease heterozygote detection: a component of population screening for Tay-Sachs disease carriers. II. Sandhoff disease gene frequencies in American Jewish and non-Jewish populations. Am J Hum Genet. 1987 Jul;41(1):16-26.
• Myerowitz R, Hogikyan ND. Different mutations in Ashkenazi Jewish and non-Jewish French Canadians with Tay-Sachs disease. Science. 1986 Jun 27;232(4758):1646-8. doi: 10.1126/science.3754980.
• Daich Varela M, Zein WM, Toro C, Groden C, Johnston J, Huryn LA, d'Azzo A, Tifft CJ, FitzGibbon EJ. A sialidosis type I cohort and a quantitative approach to multimodal ophthalmic imaging of the macular cherry-red spot. Br J Ophthalmol. 2021 Jun;105(6):838-843. doi: 10.1136/bjophthalmol-2020-316826. Epub 2020 Aug 4.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2002

Study Registration Dates

• First Submitted: January 27, 2002
• First Submitted That Met QC Criteria: January 26, 2002
• First Posted (Estimated): January 28, 2002

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: January 5, 2024

More Information

Terms related to this study

• Keywords: Natural History; Lysosomal Storage Disorder; Tay-Sachs; Lysosomal Storage; GM1 Gangliosidosis; Sandhoff; Gaucher; GM2 Gangliosidosis; Sialidosis; Glycoprotein Disorders
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Myoclonus
• Other Study ID Numbers: 020107; 02-HG-0107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: .There is not currently a plan to make IPD available, however, after publishing trial data, a plan to share IPD may be made.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No