Elleder M
1st Hlava's Institute of Pathology, Faculty of Medicine, Prague, CSSR.
Pathol Res Pract. 1989 Sep;185(3):293-328. doi: 10.1016/S0344-0338(89)80006-8.
Results of the investigation carried out during this decade brought unambigous evidence of biochemical heterogeneity inside the complex of Niemann-Pick disease according to which two entirely different metabolic disorders can be recognized. 1. Niemann-Pick sphingomyelinosis, a clear-cut enzymopathy, the pivotal lesion of which is the deficiency of lysosomal spingomyelinase leading to widespread lysosomal deposition of sphingomyelin liquid crystals. Two main allelic variants are known. The first one, neuronopathic (former type A) known as infantile with rapid course, may also manifest considerably prolonged course or an atypical course with predominantly visceral symptomatology. Patients with the second, visceral, variant (former type B), display mainly slow clinical course and often reach adulthood. With rare exceptions the neuronopathic variant can be biochemically recognized from the visceral one by much lower values of the in vivo sphingomyelin degradation test in the former. 2. The rest of the complex comprising types C-D differs substantially from the sphingomyelinase deficiency group by the remarkable heterogeneity in the lysosomal stored lipid pattern given by differences among the affected cell populations. Sphingomyelin storage could be proved histochemically solely in the histiocytic population together with cholesterol, neutral glycosphingolipids and lysobisphosphatidic acid, whereas the brain neurons displayed only neutral glycosphingolipid storage. There is an increasing evidence of the crucial biochemical lesion in this group being an altered intracellular traffic of exogenously derived cholesterol caused probably by its deficient translocation from lysosomes to other intracellular membrane sites. This leads to decreased cholesterol esterification rate which is the basis of the newly developed diagnostic test. Inconstant depression of sphingomyelinase activity is considered to be a secondary phenomenon. The so-called lactosylceramidosis is a rare variant pertinent to this group. The biochemical nature of type E still awaits clarification. Both groups of Niemann-Pick disease display clinical and especially histochemical features which allows to establish diagnosis in a highly efficient way already at the clinicopathological level.
在这十年间开展的调查结果提供了明确证据，表明尼曼-皮克病复合体内部存在生化异质性，据此可识别出两种截然不同的代谢紊乱。1. 尼曼-皮克鞘磷脂沉积病，一种明确的酶病，其关键病变是溶酶体鞘磷脂酶缺乏，导致鞘磷脂液晶在溶酶体中广泛沉积。已知有两个主要的等位基因变体。第一个是神经病变型（以前的A型），以婴儿期发病、病程迅速为特征，也可能表现为病程显著延长或主要以内脏症状为主的非典型病程。第二个是内脏型变体（以前的B型），患者主要表现为临床病程缓慢，常能活到成年。除极少数例外，通过体内鞘磷脂降解试验中前者的值远低于后者，可从生化角度将神经病变型变体与内脏型变体区分开来。2. 复合体中其余的C - D型与鞘磷脂酶缺乏组有很大不同，其溶酶体储存脂质模式存在显著异质性，这是由受影响细胞群体之间的差异所致。仅在组织细胞群体中通过组织化学方法可证实鞘磷脂与胆固醇、中性糖鞘脂和溶血双磷脂酸一起储存，而脑神经元仅显示中性糖鞘脂储存。越来越多的证据表明，该组的关键生化病变是外源性胆固醇的细胞内运输改变，这可能是由于其从溶酶体向其他细胞内膜位点的转运不足所致。这导致胆固醇酯化率降低，这是新开发的诊断测试的基础。鞘磷脂酶活性的不恒定降低被认为是一种继发现象。所谓的乳糖神经酰胺沉积病是与该组相关的一种罕见变体。E型的生化性质仍有待阐明。尼曼-皮克病的两组均表现出临床特征，尤其是组织化学特征，这使得在临床病理水平上就能高效地做出诊断。
