Protocol Number: 02-DK-0107

Title:

Investigation of Neurodegeneration in Glycosphingolipid Storage Disorders

Number:

02-DK-0107

Summary:

This study will evaluate children with glycosphingolipid (GSL) storage disorders to investigate brain changes that cause nervous system degeneration. No experimental treatments are offered in this study; participants will receive standard medical care for their disease. The information from this study may help researchers develop new therapies for these disorders and monitor the effects of treatment.

Patients of any age with Tay-Sachs disease, Sandhoff disease, GM1 gangliosidosis, or type 2 Gaucher disease may be eligible for this study.

Participants will be admitted to the NIH Clinical Center for 4 to 5 days every 6 months for a clinical evaluation involving the following tests and procedures:

- Medical history

- Physical, neurologic, and eye examinations

- Developmental evaluations by a physical therapist, nutritionist and psychologist

- Blood tests to check nutritional status, liver and kidney function, and, in patients treated for seizures, level of anti-seizure drugs. Some blood will also be used for research purposes.

- Urinalysis to check urine sugar levels and kidney function

- Skin biopsy to obtain cells to grow in culture. The biopsy area is numbed with an anesthetic cream and a 1/8-inch piece of skin is removed with a circular punch and scissors.

- Genetic analysis of DNA to screen for mutations responsible for the patient's GSL storage disorder

- Magnetic resonance imaging (MRI) brain scans. Children with type 2 Gaucher disease, Sandhoff disease and GM1 gangliosidosis will also have liver and spleen scans. Brain scans will be done every 6 months the first year. After that, they may be done less often, depending on the results. For the MRI, the child lies still in a narrow cylinder (the scanner). A magnetic field and radio waves are used to produce pictures of the organs under study. (Children will be sedated for MRI. Children who cannot be sedated will not have this test.)

- Electroencephalogram (EEG) to measure electrical activity of the brain and detect possible seizures. For this test, electrodes (small metal discs attached to wires) are attached to the child's head with a paste and the brain waves (electrical activity) are recorded while the child rests quietly.

- Brainstem auditory evoked response (BAER) to measure hearing. Electrodes are attached to the child's head (similar to the EEG procedure) and the brain waves are recorded when a sound stimulation is given.

- Lumbar puncture (spinal tap) to study proteins in the cerebrospinal fluid, which bathes the brain and spinal cord. A needle is inserted in the space between the bones (vertebrae) in the lower back. About 2 tablespoons of fluid is collected through the needle. This test is done under anesthetic at the same time the MRI is done. If the child cannot be sedated, a local anesthetic will be used.

Sponsoring Institute:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION/EXCLUSION CRITERIA:

Subject Selection: Any patient with biochemically confirmed infantile or juvenile Tay-Sachs, Sandhoff, or GM1 gangliosidosis or type 2 Gaucher disease will be accepted into this study.

No exclusions will be based on race or gender. Both sexes will be recruited.

Patients will be recruited without regard to ethnic group, however the gene frequency of Tay-Sachs is higher in individuals of Ashkenazi Jewish descent and Sandhoff disease may be higher in the Hispanic population.

Patients will be excluded if they cannot travel to the NIH because of their medical condition.

Patients will be excluded if they are unable to undergo MRI/MRS imaging for the following reasons:

-Implanted cardiac pacemaker or autodefibrillator

-Implanted neural pacemaker

-Cochlear implants

-Metallic foreign bodies in the eye or central nervous system (such as an aneurysmal clip)

-Any form of implanted wire or metal device that may concentrate radio frequency fields

-History of an adverse reaction to sedation or anesthesia

-Determination by the anesthesiologist that they are too medically fragile to undergo sedation or anesthesia for the MRI.

Special Instructions:

Currently Not Provided

Keywords:

Tay-Sachs

Sandhoff

Gaucher

GM1 Gangliosidosis

Lysosomal Storage

Recruitment Keyword(s):

Lysosomal Storage Disorder

Tay-Sachs

Sandhoff

Gaucher

Condition(s):

Gangliosidoses

Gaucher Disease

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Diabetes and Digestive and Kidney Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

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.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

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