Different molecular mechanisms leading to white matter hypomyelination in infantile onset lysosomal disorders
Different molecular mechanisms leading to white matter hypomyelination in infantile onset lysosomal disorders
复制标题
DOI：
10.1055/s-2005-865863
复制
发表时间：
2005-08-01
期刊：
影响因子：
1.4
通讯作者：
Biancheri, R
中科院分区：
文献类型：
--
作者：
Di Rocco, M;Rossi, A;Biancheri, R
低髓鞘性脑白质病可能与髓鞘形成的原发障碍有关，也可能由神经元、少突胶质细胞或星形胶质细胞功能障碍引起，导致髓鞘形成失败。与少突胶质细胞直接代谢损伤相关的异常髓鞘形成已被证明发生在溶酶体贮积病的一些动物模型中。为了证明早发性溶酶体贮积病也可能发生在人类中，我们报告了3例婴儿发病的溶酶体贮积病（1型GM1神经节脂质沉积症，球状细胞白质营养不良或克拉伯病，和A型尼曼-皮克病），表现为白质低髓质化。因此，髓鞘化低白质脑病可能代表溶酶体贮积障碍的一个特征，发病于生命最初几个月，此时髓鞘形成过程特别活跃，表明神经元贮积障碍可能是中枢神经系统髓鞘化低的主要原因。
Hypomyelinating leukoencephalopathies may be related to a primary disturbance in the formation of myelin or may be caused by neuronal, oligodendrocytic or astrocytic dysfunction, leading to a failure of myelination. Abnormal myelination related to a direct metabolic damage on oligodendrocytes has been shown to occur in some animal models of lysosomal storage diseases. To demonstrate that cerebral white matter hypomyelination may occur also in humans affected by early-onset lysosomal storage diseases, we report three cases with infantile-onset lysosomal storage disorders (type 1 GM1 gangliosidosis, globoid cell leukodystrophy or Krabbe's disease, and type A Niemann-Pick disease) showing white matter hypomyelination. Hypomyelinating leukoencephalopathy may therefore represent a feature of lysosomal storage disorders with onset in the first months of life, when the process of myelination is particularly active, indicating that neuronal storage disorders may be primarily responsible for central nervous system hypomyelination.