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The Classification and Cause of Leukodystrophies of Unknown Cause

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00001671
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : July 2, 2017
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

Leukodystrophy is a disease of the white matter of the brain. White matter is the portion of the brain responsible for conducting electrical impulses from one area of the brain to the other. Insulating cells called myelin cover the brain and nerve cells in the white matter. If myelin becomes damaged electrical information cannot be transferred properly.

Many patients suffering from leukodystrophies do not fit the description of any of the defined types of leukodystrophies and are therefore considered to have a leukodystrophy of unknown cause.

The purpose of this study is to define groups of patients with leukodystrophies and to work toward finding the cause of the disorders. In order to do this, researchers will analyze patients with leukodystrophies of unknown causes. Patients will undergo clinical, neurophysiologic, biochemical, and genetic examinations and tests.

Researchers believe that by studying these patients and their disorders they will be able to better understand the causes of myelin destruction, and eventually lead to effective treatments for these disorders.

Condition or disease
Lysosomal Storage Disease

Detailed Description:
Patients with leukodystrophies (LDs) of unknown etiology are a heterogeneous group but constitute the second largest group of genetic white matter diseases. The purpose of this study is to: (a) define novel homogeneous groups of patients with LDs and (b) work toward finding the cause of these disorders. In order to achieve these goals, patients with LDs of unknown cause will be analyzed clinically, neurophysiologically, biochemically and genetically. Patients would have been diagnosed as having no known leukodystrophies at outside centers. At the Clinical Center, such patients will undergo a series of neuropsychological, blood, urine, spinal fluid, radiological, and peripheral tissue pathological tests. Some of these tests will be part of a standard battery while others will be tailored to individual patients. Patients will be followed for 3 years. Patients will be screened for mutations in genes coding for structural myelin proteins. In some patients in whom all tests yielded no information regarding the etiology of their disease, open brain biopsy will be considered. Brain biopsy tissue will be evaluated using a novel combination of approaches including detailed pathological, immunohistochemical, and biochemical analysis of myelin proteins and lipids. Oligodendroglial biology and expression of myelin genes in the brain will also be investigated in situ. It is hoped that the present study will help clarify the nosology of the leukodystrophies and significantly advance our understanding of the pathogenesis of these diseases.

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Study Type : Observational
Enrollment : 400 participants
Official Title: The Nosology and Etiology of Leukodystrophies of Unknown Cause
Study Start Date : September 9, 1997
Study Completion Date : December 15, 2008

Resource links provided by the National Library of Medicine

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

    1. Candidates for participation in the protocol will be patients of all ages with clinical and radiographic signs of leukodystrophy who do not have a specific etiology despite a previous comprehensive workup. The preceding investigation would have excluded the following: adrenoleukodystrophy, adrenomyeloneuropathy, metachromatic leukodystrophy, Krabbe disease, Canavan disease, a well-defined amino acid organic acid disorder, or a systemic mitochondrial cytopathy.
    2. First -degree relatives of patients with leukodystrophies of unknown etiology (father, mother, siblings, or sons and daughters of the patients)


  1. Refusal to sign the protocol consent form.
  2. Candidates who are unable to travel to the National Institutes of Health Clinical Center.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00001671

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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, District of Columbia
Childrens National Medical Center
Washington, D.C., District of Columbia, United States
Institut National de la Sante' et de la Recherche Medicale
Clermont-Ferrand, Cedex, France, 63001
Tel Aviv University
Tel Aviv, Israel
Academiseh Ziuekenhuis Vrije Universiteit
Amsterdam, Netherlands
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00001671    
Other Study ID Numbers: 970170
First Posted: November 4, 1999    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: December 15, 2008
Keywords provided by National Institutes of Health Clinical Center (CC):
White Matter
Degenerative Diseases
Additional relevant MeSH terms:
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Lysosomal Storage Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases