The Nosology and Etiology of Leukodystrophies of Unknown Causes

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 sta