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Protocol Details

Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

02-HG-0107

Sponsoring Institute

National Human Genome Research Institute (NHGRI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 1 days
Max Age: 100 Years

Referral Letter Required

No

Population Exclusion(s)

None

Keywords

Sialidosis;
Lysosomal Storage;
GM1 Gangliosidosis;
GM2 Gangliosidosis;
Natural History;
Glycoprotein Disorders

Recruitment Keyword(s)

Lysosomal Storage Disorder;
Tay-Sachs;
Sandhoff;
Gaucher

Condition(s)

Neurological Regression;
Myoclonus;
Cherry Red Spot;
Brain Atrophy

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Human Genome Research Institute

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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Eligibility

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


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Citations:

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.

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.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Cynthia J. Tifft, M.D.
National Human Genome Research Institute (NHGRI)
NIHBC 10 - CRC BG RM 3-2551
10 CENTER DR
BETHESDA MD 20892
(301) 451-8485
cynthiat@mail.nih.gov

Jean M. Johnston
National Human Genome Research Institute (NHGRI)
National Institutes of Health
Building 10
Room 3-2551
10 Center Drive
Bethesda, Maryland 20892
(240) 515-1448
johnstonjm@mail.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT00029965

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