遗传性共济失调的复杂临床与基因分类。II. 常染色体隐性共济失调
The complex clinical and genetic classification of inherited ataxias. II. Autosomal recessive ataxias.
作者信息
Di Donato S, Gellera C, Mariotti C
机构信息
Division of Biochemistry and Genetics, C. Besta National Neurological Institute, Via Celoria 11, I-20133 Milan, Italy.
出版信息
Neurol Sci. 2001 Jun;22(3):219-28. doi: 10.1007/s100720100017.
Autosomal recessive ataxias are a heterogeneous group of rare neurodegenerative diseases characterized by early onset cerebellar ataxia associated with various neurologic, ophthalmologic and systemic signs. In comparison with autosomal dominant ataxias, the group of recessive ataxias is less extensively characterized. In fact, only a few conditions have been genetically characterized. The pathogenesis of these forms is associated with a "loss of function" of specific cellular proteins involved in metabolic homeostasis, cell cycle, and DNA repair/protection processing. The two most common autosomal recessive ataxias, in European countries, are Friedreich's ataxia and ataxia telangiectasia. Other forms are much less frequent, and include ataxia with vitamin E deficiency, abetalipoproteinemia. Refsum's disease, spastic ataxia, infantile onset spinocerebellar ataxia, and ataxia with oculomotor apraxia. These pathological conditions, although extremely rare, have nevertheless to be carefully considered in differential diagnosis, not only for correct nosographical classification, but particularly, for specific prognostic and therapeutic implications. Some of these diseases exhibit a peculiar regional distribution. An updated review of the clinical, genetic, and pathogenic aspects of recessive ataxias is presented. Specific management problems with respect to diagnosis and genetic counseling are discussed.
常染色体隐性共济失调是一组异质性罕见神经退行性疾病,其特征为早期出现小脑共济失调,并伴有各种神经、眼科和全身症状。与常染色体显性共济失调相比,隐性共济失调组的特征描述较少。事实上,只有少数疾病在基因层面得到了特征描述。这些疾病的发病机制与参与代谢稳态、细胞周期及DNA修复/保护过程的特定细胞蛋白的“功能丧失”有关。在欧洲国家,最常见的两种常染色体隐性共济失调是弗里德赖希共济失调和共济失调毛细血管扩张症。其他类型则更为罕见,包括维生素E缺乏性共济失调、无β脂蛋白血症、雷夫叙姆病、痉挛性共济失调、婴儿期起病的脊髓小脑共济失调以及伴有动眼性失用的共济失调。这些病理状况尽管极为罕见,但在鉴别诊断中仍需仔细考虑,不仅是为了正确的疾病分类,特别是为了明确特定的预后和治疗意义。其中一些疾病呈现出特殊的区域分布。本文对隐性共济失调的临床、基因和致病方面进行了最新综述,并讨论了诊断和遗传咨询方面的具体管理问题。