Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred

摘要: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare autosomal dominant disorder characterized by cerebral white matter degeneration axonal leading to progressive cognitive and motor dysfunction. We report clinical pathological features, as well molecular genetic analysis, of family HDLS. A pedigree consisting 27 persons in 5 generations contained 6 affected individuals. Dementia depression were common; two individuals presented syndrome resembling corticobasal (CBD). Postmortem neuropathologic evaluation three revealed enlargement the lateral ventricles marked attenuation matter, but preservation brainstem cerebellum, except for corticospinal tract. Histopathologic studies showed loss myelinated fibers, lipid-laden macrophages bizarre astrocytes, abundant that immunoreactive phosphorylated neurofilament protein amyloid precursor (APP), not αB-crystallin variably ubiquitin. By electron microscopy, aggregates intermediate filaments or organelles predominantly vesicular lamellar. The cortex had focal neuronal αB-crystallin-immunoreactive ballooned neurons. In summary, present describes previously unreported kindred HDLS presenting CBD. Immunohistochemistry APP demonstrates distinctive neurodegeneration axons perikarya.