Northern epilepsy:: A novel form of neuronal ceroid-lipofuscinosis
Northern epilepsy:: A novel form of neuronal ceroid-lipofuscinosis
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DOI：
10.1111/j.1750-3639.2000.tb00255.x
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发表时间：
2000-04-01
期刊：
影响因子：
6.4
通讯作者：
Haltia, M
中科院分区：
文献类型：
--
作者：
Herva, R;Tyynelä, J;Haltia, M
北方癫痫是一种常染色体隐性儿童发作性癫痫综合征，临床特征是5~10岁时出现全身性强直阵挛发作，随后缓慢进行性智力恶化。患者的年龄可能达到50或60岁。最近在染色体8p23上的一个新基因中发现了导致该病的突变，该基因编码一种功能未知的膜蛋白。本研究基于3名尸检患者的基础上，首次对该病进行了神经病理学分析，并显示胞浆内自发荧光颗粒在神经元内聚集。石蜡切片中的颗粒经Luxol坚蓝、高碘酸席夫和苏丹黑B法染色，线粒体ATP合成酶c亚单位和鞘磷脂激活蛋白A和D呈免疫阳性反应。神经元内存储具有高度的选择性：等皮质第三层和海马CA2、CA3和CA4区受到严重影响，而等皮质其他层、CA1区和小脑皮质仅轻微受累。膜结合型贮藏细胞体的超微结构呈曲线状，含有一些颗粒状成分，Western blotting和纯化后的贮藏材料的N-末端序列分析表明，c亚基是主要成分。这些发现确定北方癫痫是一种新的神经性蜡样脂褐素沉积症，病程异常漫长。
Northern epilepsy is an autosomal recessive childhood onset epilepsy syndrome, clinically characterized by generalized tonic-clonic seizures with onset at 5 to 10 years of age and subsequent slowly progressive mental deterioration. The patients may reach 50 or 60 years of age. A mutation responsible for the disease has recently been identified in a novel gene on chromosome 8p23, encoding a putative membrane protein with an unknown function, The present study, based on three autopsied patients, is the first neuropathological analysis of the disease, and showed intraneuronal accumulation of cytoplasmic autofluorescent granules. The granules were strongly stained by the Luxol fast blue, periodic acid-Schiff, and Sudan black B methods in paraffin sections, and were immunoreactive for subunit c of the mitochondrial ATP synthase and sphingolipid activator proteins A and D. The intraneuronal storage was highly selective: the third layer of the isocortex and the hippocampal CA2, CA3, and CA4 sectors were severely affected, while other layers of the isocortex, the CA1 sector, and the cerebellar cortex were only minimally involved. The membrane-bound storage cytosomes showed a curvilinear ultrastructure with admixture of some granular components, Western blotting and N-terminal sequence analysis of purified storage material identified subunit c as the major component. These findings establish Northern epilepsy as a new form of neuronal ceroid-lipofuscinosis with an exceptionally protracted course.