Childhood ataxia with diffuse central nervous system hypomyelination

Authors

  • Dr. Raphael Schiffmann MD,

    Corresponding author
    1. Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
    • National Institutes of Health, Building 10, Room 3D03, 9000 Rockville Pike, Bethesda, MD 20892
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  • Johanna R. Moller MD,

    1. Laboratory of Molecular and Cellular Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Bruce D. Trapp PhD,

    1. Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Henry H-L. Shih MD,

    1. Neuroimaging Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Robert G. Farrer PhD,

    1. Laboratory of Molecular and Cellular Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • David A. Katz MD,

    1. Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Jeffry R. Alger PhD,

    1. Neuroimaging Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Colette C. Parker MD,

    1. Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Peter E. Hauer BS,

    1. Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Christine R. Kaneski BS,

    1. Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • John D. Heiss MD,

    1. Department of Neurology, Johns Hopkins University, Baltimore, MD
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  • Edward M. Kaye MD,

    1. Division of Pediatric Neurology, Tufts, New England Medical Center, Boston, MA
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  • Richard H. Quarles PhD,

    1. Laboratory of Molecular and Cellular Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Roscoe O. Brady MD,

    1. Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Norman W. Barton MD, PhD

    1. Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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Abstract

A significant number of patients with progressive leukodystrophy do not have a definitive diagnosis. This report describes the clinical, morphological, and biochemical characteristics of 4 unrelated girls with progressive ataxic diplegia of unknown etiology. These patients had normal development until the ages of 1.5 to 5 years. A diffuse confluent abnormality of the white matter of the central nervous system was present on computed tomography and magnetic resonance scans obtained early in the course of the illness. Dementia was not present and peripheral nerves were normal. All patients were evaluated for known metabolic and degenerative diseases and no abnormalities were observed. Light and electron microscopy of open-brain biopsy specimens from 2 girls showed selective white matter abnormalities including hypomyelination, demyelination, and gliosis. Myelin-specific proteins in the subcortical white matter were examined immunocytochemically and by Western blot analysis. The were of normal molecular size but were markedly reduced in quantity in both patients compared to control subjects. Lipid analysis revealed decreased levels of characteristic myelin lipids. When examined by magnetic resonance spectroscopic imaging, all patients showed a marked decrease of N-acetylaspartic acid, choline, and creatine in white matter only. The magnetic resonance spectroscopic imaging profile is a unique diagnostic feature of this clinicopathological syndrome.

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