Leukodystrophy in patients with ovarian dysgenesis
Corresponding Author
Dr Raphael Schiffmann MD
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, Cleveland, OH
NIH, Building 10, Room 3D03, 9000 Rockville Pike, Bethesda, MD 20892–1260Search for more papers by this authorGioacchino Tedeschi MD
Neuroimaging Branch, National Institute of Neurological Disorders and Stroke, Cleveland, OH
Search for more papers by this authorR. Philip Kinkel MD
Departments of Neurology, The Cleveland Clinic Foundation, Cleveland, OH
Search for more papers by this authorBruce D. Trapp PhD
Departments of Neurosciences, The Cleveland Clinic Foundation, Cleveland, OH
Search for more papers by this authorJoseph A. Frank PhD
Laboratory of Diagnostic Radiology, National Institute of Child Health and Human Development, Office of the Director, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, Cleveland, OH
Search for more papers by this authorChristine R. Kaneski MS
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, Cleveland, OH
Search for more papers by this authorRoscoe O. Brady MD
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, Cleveland, OH
Search for more papers by this authorNorman W. Barton MD, PhD
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, Cleveland, OH
Search for more papers by this authorLawrence Nelson MD
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Office of the Director, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, Cleveland, OH
Search for more papers by this authorJack A. Yanovski MD, PhD
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Office of the Director, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, Cleveland, OH
Search for more papers by this authorCorresponding Author
Dr Raphael Schiffmann MD
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, Cleveland, OH
NIH, Building 10, Room 3D03, 9000 Rockville Pike, Bethesda, MD 20892–1260Search for more papers by this authorGioacchino Tedeschi MD
Neuroimaging Branch, National Institute of Neurological Disorders and Stroke, Cleveland, OH
Search for more papers by this authorR. Philip Kinkel MD
Departments of Neurology, The Cleveland Clinic Foundation, Cleveland, OH
Search for more papers by this authorBruce D. Trapp PhD
Departments of Neurosciences, The Cleveland Clinic Foundation, Cleveland, OH
Search for more papers by this authorJoseph A. Frank PhD
Laboratory of Diagnostic Radiology, National Institute of Child Health and Human Development, Office of the Director, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, Cleveland, OH
Search for more papers by this authorChristine R. Kaneski MS
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, Cleveland, OH
Search for more papers by this authorRoscoe O. Brady MD
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, Cleveland, OH
Search for more papers by this authorNorman W. Barton MD, PhD
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, Cleveland, OH
Search for more papers by this authorLawrence Nelson MD
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Office of the Director, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, Cleveland, OH
Search for more papers by this authorJack A. Yanovski MD, PhD
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Office of the Director, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, Cleveland, OH
Search for more papers by this authorAbstract
We describe clinical, biochemical, pathological, and spectroscopic findings in 4 women, aged 15 to 29 years, from three unrelated families who had a unique combination of a central neurvous system white matter disease and primary ovarian failure. All had normal initial development but 3 had borderline low IQ and academic difficulties in primary school. Puberty did not develop in 2 patients and was arrested in a third patient. The fourth patient had premature ovarian failure at the age of 13 years. Head magnetic resonance imaging showed diffuse white matter disease, with frontal cortical atrophy in the most clinically advanced patient. All patients had normal karyotype and normal findings on extensive evaluations for known leukodystrophies, for other metabolic diseases, and for causes of ovarian failure. Proton magnetic resonance spectroscopic imaging showed reduction of choline-containing compounds in the affected white matter in all patients and reduction of N-acetylaspartate in the unaffected frontal white matter of 2 patients. All patients had evidence of primary gonadal insufficiency with a normal hypothalamic-hypophyseal axis. Pathological analysis showed streak ovaries in 1 patient and signs of hypomyelination, and gliosis on brain biopsy in another patient. In conclusion, we present a novel group of patients who have in common leukodystrophy, primary ovarian dysfunction, and magnetic resonance spectroscopic abnormalities.
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