Martin J J, Lowenthal A, Ceuterick C, Vanier M T
J Neurol Sci. 1984 Oct;66(1):33-45. doi: 10.1016/0022-510x(84)90139-4.
In two siblings affected with dementia, epilepsy and vertical supranuclear ophthalmoplegia, foam cells and sea-blue histiocytes were found in the bone marrow. Electron microscopy of skin and neuromuscular biopsies gave presumptive evidence in favour of a storage disorder. Postmortem examination of both cases revealed an intraneuronal polymorphous lysosomal storage in the central nervous system (in the cortex and in many nuclei e.g. the substantia nigra and the reticular formation of the brain stem). In the visceral organs with the spleen most severely affected, the inclusions had a different ultrastructure, being composed of tightly apposed leaflets. The biochemical study revealed accumulation of sphingomyelin and other lipids in liver and spleen, with normal sphingomyelinase activities, which is consistent with the diagnosis of Niemann-Pick disease type C. In the brain, the most striking abnormalities involved the glycolipids. Sphingomyelinase activities were unchanged in cultivated skin fibroblasts. These data compared with those of reported cases, allowed the following conclusions to be made: (1) although the combination of clinical features appears to be unique, none of them, when considered separately, is pathognomonic for juvenile dystonic lipidosis; (2) diagnosis during life can be suggested by careful examination of nerve bundles and fibroblasts with the electron microscope, although the method of choice appears to be the study of bone marrow; but final assessment of the diagnosis, in the absence of demonstrable enzymic deficiency, requires in most cases a study of the lipid profile in a liver biopsy (or better, spleen tissue whenever available); (3) the intralysosomal storage is different, both morphologically and biochemically, in the central nervous system and in the spleen; (4) juvenile dystonic lipidosis represents a juvenile variant of Niemann-Pick disease type C, pending the discovery of the primary defect responsible for this disorder.
在两名患有痴呆、癫痫和垂直性核上性眼肌麻痹的兄弟姐妹中，骨髓中发现了泡沫细胞和海蓝色组织细胞。皮肤和神经肌肉活检的电子显微镜检查提供了支持贮积症的初步证据。对这两个病例的尸检显示，中枢神经系统（皮质以及许多核团，如黑质和脑干网状结构）存在神经元内多形性溶酶体贮积。在内脏器官中，脾脏受影响最严重，内含物具有不同的超微结构，由紧密相邻的薄片组成。生化研究显示，肝脏和脾脏中鞘磷脂和其他脂质蓄积，鞘磷脂酶活性正常，这与尼曼-匹克病C型的诊断一致。在大脑中，最显著的异常涉及糖脂。培养的皮肤成纤维细胞中的鞘磷脂酶活性未改变。将这些数据与报道病例的数据进行比较后，可得出以下结论：（1）尽管临床特征的组合似乎是独特的，但单独考虑时，它们中没有一个对青少年肌张力障碍性脂质沉积症具有诊断特异性；（2）尽管首选方法似乎是骨髓研究，但通过仔细的神经束和电子显微镜下的成纤维细胞检查，生前诊断仍可被提示；但在缺乏可证实的酶缺乏的情况下，大多数病例的最终诊断评估需要对肝活检（或更好的是，如有可用的脾组织）进行脂质谱研究；（3）溶酶体内贮积在中枢神经系统和脾脏中在形态和生化方面均不同；（4）青少年肌张力障碍性脂质沉积症代表尼曼-匹克病C型的青少年变异型，有待发现导致该疾病的主要缺陷。
