title: Leukodystrophy in patients with ovarian dysgenesis.
abstract: 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 nervous 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.
authors.affiliation: Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1260, USA.
authors.forename: R
authors.initials: R
authors.lastname: Schiffmann
authors.forename: G
authors.initials: G
authors.lastname: Tedeschi
authors.forename: R P
authors.initials: RP
authors.lastname: Kinkel
authors.forename: B D
authors.initials: BD
authors.lastname: Trapp
authors.forename: J A
authors.initials: JA
authors.lastname: Frank
authors.forename: C R
authors.initials: CR
authors.lastname: Kaneski
authors.forename: R O
authors.initials: RO
authors.lastname: Brady
authors.forename: N W
authors.initials: NW
authors.lastname: Barton
authors.forename: L
authors.initials: L
authors.lastname: Nelson
authors.forename: J A
authors.initials: JA
authors.lastname: Yanovski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D002648:Child; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D004569:Electroencephalography; D005260:Female; D006059:Gonadal Dysgenesis / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D009460:Neurologic Examination; D010053:Ovary / Q000002:abnormalities* / Q000473:pathology; D010901:Pituitary Function Tests