Clinical Trial: Nervous System Degeneration in Glycosphingolipid Storage Disorders

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Investigation of Neurodegeneration in the Glycosphingolipid Storage Disorders

Brief 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.
  

  Detailed Summary:

  The GM1 and GM2 gangliosidoses are lysosomal storage disorders that primarily affect the brain and are uniformly fatal. 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 in order 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 in affected individuals of all ages, races and genders using medical technologies including MRI/MRS, hearing evaluation and auditory evoked response testing, and EEG, as well as subspecialty evaluations in rehabilitative medicine, ophthalmology, speech language pathology, neurology, and psychology. Biomarkers of disease progression will be explored in CSF and blood samples for correlation with disease staging. Fibroblast cultures will be established for testing potential therapeutic agents. 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 will 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 will be sent to families who do not wish to undergo clinical evaluation at the NIH, who are too unstable to travel, or whose children are already deceased.

  
  Sponsor: National Human Genome Research Institute (NHGRI)
  

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  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: January 27, 2002
  Date Started: January 23, 2002
  Date Completion:
  Last Updated: April 26, 2017
  Last Verified: April 14, 2017