Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred
Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred
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DOI：
10.1007/s00401-006-0046-z
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发表时间：
2006-04-01
影响因子：
12.7
通讯作者：
Wszolek, ZK
中科院分区：
文献类型：
--
作者：
Baba, Y;Ghetti, B;Wszolek, ZK
遗传性弥漫性白质脑病伴球状体（HDLS）是一种罕见的常染色体显性遗传病，其特征是伴有轴突球状体的大脑白色变性，导致进行性认知和运动功能障碍。我们报告一个HDLS家族的临床和病理特征，以及分子遗传学分析。一个由5代27人组成的家系包含6个患病个体。痴呆症和抑郁症是常见的;两个人提出了类似皮质基底节变性（CBD）的综合征。三个受影响的人死后的神经病理学评价显示侧脑室扩大和大脑白色物质显着衰减，但保留白色物质在脑干和小脑，除了皮质脊髓束。组织学研究表明，有髓纤维，脂质负载的巨噬细胞和奇异的星形胶质细胞，以及丰富的轴突球状体的磷酸化神经丝蛋白和淀粉样前体蛋白（APP）的免疫反应，但不是α B-晶体蛋白和泛素。通过电子显微镜，轴突球体包含聚集的中间丝或细胞器，主要是囊泡和层状。大脑皮质有局灶性神经元变性，伴有α B-晶状体蛋白免疫反应阳性气球样神经元。总之，本报告描述了一个以前未报告的亲属HDLS与个人提出的CBD。APP和α B-晶体蛋白的免疫组织化学显示大脑轴突和胞体中有明显的神经变性。
Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare autosomal dominant disorder characterized by cerebral white matter degeneration with axonal spheroids leading to progressive cognitive and motor dysfunction. We report clinical and pathological features, as well as molecular genetic analysis, of a family with HDLS. A pedigree consisting of 27 persons in 5 generations contained 6 affected individuals. Dementia and depression were common; two individuals presented with a syndrome resembling corticobasal degeneration (CBD). Postmortem neuropathologic evaluation of three affected individuals revealed enlargement of the lateral ventricles and marked attenuation of cerebral white matter, but preservation of white matter in brainstem and cerebellum, except for the corticospinal tract. Histopathologic studies showed a loss of myelinated fibers, lipid-laden macrophages and bizarre astrocytes, as well as abundant axonal spheroids that were immunoreactive for phosphorylated neurofilament protein and amyloid precursor protein (APP), but not alpha B-crystallin and variably with ubiquitin. By electron microscopy, axonal spheroids contained aggregates of intermediate filaments or of organelles that were predominantly vesicular and lamellar. The cerebral cortex had focal neuronal degeneration with alpha B-crystallin-immunoreactive ballooned neurons. In summary, the present report describes a previously unreported kindred with HDLS with individuals presenting as CBD. Immunohistochemistry for APP and alpha B-crystallin demonstrates distinctive neurodegeneration in cerebral axons and perikarya.