Protocol Number: 09-HG-0128

Title:

Leukodystrophies of Unknown Cause

Number:

09-HG-0128

Summary:

Background:

- A leukodystrophy is a disease affecting the white matter of the brain. The white matter conducts electricity from one part of the brain to the other. If the insulation, or myelin, is damaged, the brain's electrical pathways will not work properly. Researchers are trying to identify what causes leukodystrophy.

Objectives:

- To collect detailed clinical characterizations, including histories, physical examinations, biochemical tests, genetic studies, and neurophysiologic and neuroimaging studies in patients with unclassified leukodystrophies to comprehensively characterize such patients and obtain comparative clinical profiles.

- To collect detailed clinical characterizations, including histories, physical examinations, biochemical tests, genomic and proteomic tissue, and neurophysiologic and neuroimaging studies in patients with known leukodystrophies to investigate the underlying pathogenesis of these disorders.

- To better understand leukodystrophies of unknown cause and to identify the part of the DNA of the patient with leukodystrophy that is causing the problem.

Eligibility:

- Any individual with a known or suspected leukodystrophy is eligible to participate in this protocol, including-

---- Patients with white matter disease that is unclassified or of unknown cause, including but not limited to leukoencephalopathies with calcifications, leukoencephalopathies with cysts, leukoencephalopathies with hypomyelination, and leukoencephalopathies with brainstem involvement.

---- Parents or siblings of these subjects.

- Exclusion criteria include patients too ill to travel to the Clinical Center and patients for whom the leukoencephalopathy is felt to be secondary to an acquired cause (for example, traumatic or infectious).

Design:

- Patients will be seen either as an inpatient or outpatient depending on the tests that are planned. Patients may need to stay at the Clinical Center for 3 to 5 days.

- The following tests will be conducted as part of standard clinical care:

---- Physical and neurological examinations, including blood and urine tests.

---- Magnetic resonance-based studies to produce a picture of the patient's brain (under general anesthesia).

---- Spinal tap to measure chemicals in the spinal fluid (under general anesthesia in young children).

---- Nerve biopsy, if the peripheral nerves are affected, or muscle biopsy, if the cells called the mitochondria or the muscles are involved (both under general anesthesia).

- The following studies may be performed as part of participation in the research:

---- Blood, urine, spinal fluid, or muscle to understand the proteins, DNA, and molecules in these tissues.

---- Skin biopsy to grow (in culture) skin cells and to analyze the skin microscopically.

---- DNA studies to find new genes responsible for leukodystrophies and to better understand these diseases.

- Participation should be based on an interest to help further the research on leukodystrophies. Specific information about a patient's present or future health risks may not be gained.

Sponsoring Institute:

National Human Genome Research Institute (NHGRI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

- Patients with white matter disease that is unclassified or of unknown cause, including, but not limited to leukoencephalopathies with calcifications, leukoencephalopathies with cysts, leukoencephalopathies with hypomyelination and leukoencephalopathies with brainstem involvement.

- Parents or siblings of these subjects

EXCLUSION CRITERIA:

-Patients meeting above criteria but too ill to travel to the clinical center. In that case, consideration will be given to enrolling them for the collection of medical records and samples only.

-Patients meeting above criteria, but where the leukoencephalopathy is felt to be secondary to an acquired cause, for example traumatic or infectious.

Special Instructions:

Currently Not Provided

Keywords:

Genetic Disorders of the White Matter

Leukodystrophies

Myelin

Recruitment Keyword(s):

Leukodystrophies

White Matter Disorder

Genetic Disorder

Condition(s):

Leukodystrophy

Leukoencephalopathy

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Human Genome Research Institute

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):

Linnankivi TT, Autti TH, Pihko SH, Somer MS, Tienari PJ, Wirtavuori KO, Valanne LK.18q-syndrome: brain MRI shows poor differentiation of gray and white matter on T2-weighted images. J Magn Reson Imaging. 2003 Oct;18(4):414-9.

Gay CT, Hardies LJ, Rauch RA, Lancaster JL, Plaetke R, DuPont BR, Cody JD, Cornell JE, Herndon RC, Ghidoni PD, Schiff JM, Kaye CI, Leach RJ, Fox PT. Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency. Am J Med Genet. 1997 Jul 25;74(4):422-31.

Ugur SA, Tolun A.A deletion in DRCTNNB1A associated with hypomyelination and juvenile onset cataract. Eur J Hum Genet. 2008 Feb;16(2):261-4. Epub 2007 Oct 10.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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