Philippart M
Adv Neurol. 1978;21:131-49.
The sphingolipidoses are best defined as lysosomal storage disorders. Their manifestations can be explained on the basis of a few key principles that should all be verified before making a diagnosis. A genetic mutation may reduce the activity of a lysosomal hydrolase. Mutations of the hydrolases, respecting the active site, would not compromise their activity as tested in vitro but might interfere with the lysosomal functions. The undegraded substrates accumulate in the tissues where they are normally synthesized or taken up. The site and rate of storage define the clinical expression of the defect, which may include ataxia. Detailed, comprehensive, multidisciplinary studies emphasize the great complexity of the lysosomal storage disorders and the nonspecificity of single clinical, pathological, ultrastructural, or biochemical criteria. The possibility of inducing storage by chemical means points to aspects of the lysosomal physiology that have been neglected so far but that might also have genetic expression. Lysosomal hydrolases function in a controlled environment dependent on the lysosomal membrane, pH, and hypothetical dispersing agents. Any of these factors conceivably may be genetically impaired and give rise to apparently nonspecific storage.
鞘脂类疾病最好被定义为溶酶体贮积症。它们的表现可以基于一些关键原则来解释，在做出诊断之前，所有这些原则都应该得到验证。基因突变可能会降低溶酶体水解酶的活性。水解酶的突变，如果涉及活性位点，在体外测试时不会损害其活性，但可能会干扰溶酶体功能。未降解的底物在其正常合成或摄取的组织中积累。储存的部位和速率决定了缺陷的临床表型，这可能包括共济失调。详细、全面、多学科的研究强调了溶酶体贮积症的极大复杂性以及单一临床、病理、超微结构或生化标准的非特异性。通过化学方法诱导储存的可能性指出了溶酶体生理学中迄今为止被忽视的方面，但这些方面也可能具有遗传表达。溶酶体水解酶在依赖于溶酶体膜、pH值和假定的分散剂的可控环境中发挥作用。这些因素中的任何一个都可能在遗传上受损，并导致明显的非特异性储存。
