The Nosology and Etiology of Leukodystrophies of Unknown Causes

NCT00889174 | Completed

• 2 other identifiers: 09012809-HG-0128
• Study Type: observational
• Target: 76
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Leukodystrophy; Leukoencephalopathy

Keywords

Genetic Disorders of the White Matter; Leukodystrophies; Myelin; White Matter Disorder; Genetic Disorder

Eligibility Criteria

• Age: 1 Month - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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. doi: 10.1002/jmri.10383.

  PMID: 14508777 BACKGROUND

• 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. doi: 10.1002/(sici)1096-8628(19970725)74:43.0.co;2-k.

  PMID: 9259379 BACKGROUND

• 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. doi: 10.1038/sj.ejhg.5201935. Epub 2007 Oct 10.

  PMID: 17928815 BACKGROUND

MeSH Terms

Conditions

Leukoencephalopathies; Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• William A Gahl, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2009
• First Posted: April 28, 2009
• Study Start: April 24, 2009
• Study Completion: August 1, 2018
• Last Updated: August 3, 2018

Record last verified: 2018-08-01

Locations

US (1)