Nervous System Degeneration in Glycosphingolipid Storage Disorders
| Status: | Recruiting |
|---|---|
| Conditions: | Other Indications, Metabolic |
| Therapuetic Areas: | Pharmacology / Toxicology, Other |
| Healthy: | No |
| Age Range: | Any - 99 |
| Updated: | 3/22/2019 |
| Start Date: | January 25, 2002 |
| Contact: | Cynthia J Tifft, M.D. |
| Email: | cynthiat@mail.nih.gov |
| Phone: | (301) 451-8485 |
Investigation of Neurodegeneration in Glycosphingolipid Storage Disorders
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.
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.
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.
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.
- 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
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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