NEUROPATHOLOGY OF THE NORRBOTTNIAN TYPE OF GAUCHER DISEASE - MORPHOLOGICAL AND BIOCHEMICAL-STUDIES
NEUROPATHOLOGY OF THE NORRBOTTNIAN TYPE OF GAUCHER DISEASE - MORPHOLOGICAL AND BIOCHEMICAL-STUDIES
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DOI：
10.1007/bf00690463
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发表时间：
1984-01-01
影响因子：
12.7
通讯作者：
ERIKSON, A
中科院分区：
文献类型：
--
作者：
CONRADI, NG;SOURANDER, P;ERIKSON, A
Norrbottnian型戈谢病的特征是婴儿或青少年发病和不同程度的神经系统症状，其中一些症状仅在脾切除术后发生。这种类型的戈谢病的完整神经病理学描述尚未报告。对5例患者的脑组织进行了形态学和生化检查。在大脑和小脑皮质下白色物质（s.c.w.m.）的血管外膜中，均出现葡萄糖神经酰胺储存细胞的典型蓄积。5例病例之间在外膜储存细胞的蓄积和从s.c.w.m.分离的葡萄糖神经酰胺的脂肪酸模式方面存在差异，这暗示葡糖神经酰胺在脑中的外膜细胞中的积累依赖于广泛的脂质储存过程并且通过脾切除术而增强。2例在贮存细胞聚集区附近可见神经元和髓鞘缺失。5例均有不同程度的神经细胞丢失、卫星样变性和神经元吞噬。光镜下神经元内可见脂褐素，含有简单和复杂脂质，但无糖脂。超微结构检查发现大脑和小脑皮质、齿状核和脑桥的神经元内有双层包涵体。由于戈谢细胞内含物的双层结构，神经元中的双层被认为是由葡萄糖神经酰胺形成的。从所有病例的大脑皮层中分离的葡萄糖神经酰胺的脂肪酸组成表明，大脑神经节苷脂是其主要前体。最高水平的精神病（葡萄糖鞘氨醇）出现在最先进的神经细胞损失的情况下。形态学和生化结果表明，神经元病变过程与神经酰胺和精神病在神经元中的积累有关。
The Norrbottnian type of Gaucher disease is characterized by infantile or juvenile onset and variable degrees of neurological symptoms, some of which develop only after splenectomy. A full neuropathological description of this type of Gaucher disease has not been reported previously. The brains of 5 patients were examined morphologically and biochemically. All presented typical accumulations of glucosylceramide storing cells in the adventitia of vessels in the cerebral and cerebellar sub-cortical white matter (s.c.w.m.). There were differences between the 5 cases with regard to the accumulation of adventitial storage cells and to the fatty acid pattern of the glucosylceramide isolated from the s.c.w.m., which implicate that the accumulation of glucosylceramide in adventitial cells in the brain is dependent on the generalized lipid storage process and enhanced by splenectomy. Loss of neurons and myelin was noted in the vicinity of accumulations of storage cells in 2 cases. The 5 cases showed varying degrees of nerve cell loss, satellitosis and neuronophagia. Lipofuscin with simple and complex lipids, but no glycolipids could be demonstrated in neurons light-microscopically. Ultrastructural examination revealed inclusion bodies with bilayers in neurons of the cerebral and cerebellar cortex, dentate nucleus and pons. Because of the bilayered structure of Gaucher cell inclusions the bilayers in neurons are assumed to be formed by glucosylceramide. The fatty acid composition of glucosylceramide isolated from cerebral cortex in all cases suggested that cerebral gangliosides were its main precursor. The highest levels of psychosine (glucosylsphingosine) were seen in the cases with the most advanced nerve cell loss. The morphological and biochemical findings indicate that the neuronopathic process is associated with accumulation of glucosylceramide and psychosine in neurons.