Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders

May 28, 2026 updated by: National Human Genome Research Institute (NHGRI)

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 Overview

Status

Recruiting

Conditions

Detailed 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 establish the pattern of disease progression and to identify clinical, biochemical and biophysical markers that can be used as endpoints in future therapeutic trials.

This protocol aims to study the natural history of the GM1 and GM2 gangliosidoses, sialidosis and galactosialidosis in affected individuals of all ages, races and genders using medical technologies including MRI/MRS, hearing evaluation and auditory evoked response testing, EEG, sleep study, EMG/NCV, echocardiogram and abdominal ultrasound as well as subspecialty evaluations in rehabilitative medicine (including gait analysis), ophthalmology, speech language pathology, neurology, and psychology. Biomarkers of disease progression may be explored in CSF, blood, and urine samples for correlation with disease staging. Fibroblast cultures will be established for testing potential therapeutic agents. Some fibroblast lines will be used to create induced pluripotent stem cells (iPSC) for differentiation into neural tissues, more relevant for the study of these disorders that primarily affect the central nervous system (CNS). We hypothesize that relevant biomarkers will correlate with disease progression and will shed light on the pathophysiology of disease progression in these devastating disorders.

As a means of acquiring additional information, subjects or their parents may also be asked to complete a questionnaire regarding their medical and developmental history, initial clinical presentation of the disease and steps toward diagnosis. At their request, the same questionnaire may be sent to families who do not wish to undergo clinical evaluation at the NIH, who are medically fragile and unable to travel, or whose affected member(s) are already deceased.

We know that children with infantile GM2 gangliosidosis develop increasing macrocephaly as part of their disease. No "normal" curves for head circumference vs. age currently exist for this disorder. In an attempt to provide such curves to the clinical community parents may also be asked to provide head circumference data on their children whether they are being seen at NIH or whether a clinical questionnaire is being completed for children too medically fragile to travel or already deceased.

We know that for infantile onset disease the storage of ganglioside in neurons begins during the second trimester of pregnancy. In rare situations where carrier couples learned from prenatal diagnosis that they were carrying a fetus with infantile disease and had decided to terminate the pregnancy, we accepted samples of fetal tissue prior to June 5, 2019, for analysis of biomarkers including gene expression analysis that may lend clues as to the underlying pathogenesis of disease. This may lead to increased understanding of the early events in disease pathogenesis and suggest possible therapies.

We anticipate that information obtained from the small population of patients with glycosphingolipid and glycoprotein disorders evaluated in this study will have a broader impact on patients with other neurodegenerative lysosomal storage disorders and perhaps more common disorders of neurodegeneration.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

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 informed assent in older children may not be possible. Children with Morquio B disease are not expected to be cognitively impaired. The children with Morquio B ages 7-11 years will be asked to give verbal assent and ages 12-17 years will be asked to give written assent to the protocol. Some subjects who have reached the age of 18 may need to have legally authorized representative (usually their parents) sign consent on their behalf.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

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
Time Frame: Assessed one to every two years
Exploring the natural history of Glycoprotein Disorders
Assessed one to every two years
Natural history of Lysosomal Storage Diseases
Time Frame: Assessed one to every two years
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
Time Frame: Every 6-24 months; depending on age of subject
Evaluating change over time in eye findings.
Every 6-24 months; depending on age of subject
Audiology testing
Time Frame: Every 6-24 months; depending on age of subject
Evaluating change over time in auditory testing
Every 6-24 months; depending on age of subject
Laboratory testing
Time Frame: Every 6-24 months; depending on age of subject
Evaluating disease biomarkers over time.
Every 6-24 months; depending on age of subject
Neurology assessments
Time Frame: Every 6-24 months; depending on age of subject
Neurology assessments are done to measure change over time.
Every 6-24 months; depending on age of subject

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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)

May 29, 2026

Last Update Submitted That Met QC Criteria

May 28, 2026

Last Verified

March 16, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myoclonus

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Belgium

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe