Anheim M
Service de neurogénétique, hôpital de la Pitié-Salpêtrière, 75651 Paris, France.
Rev Neurol (Paris). 2011 May;167(5):372-84. doi: 10.1016/j.neurol.2010.07.021. Epub 2010 Nov 17.
Autosomal recessive cerebellar ataxias (ARCA) are heterogeneous and complex inherited neurodegenerative diseases that may affect the cerebellum and/or the spinocerebellar tract, the posterior column of the spinal cord and the peripheral nerves. Cerebellar ataxia is frequently proeminent and mostly associated with several neurological or extra-neurological signs, leading to a major disability before the age of 30.
Friedreich's ataxia (FRDA) is clearly the most frequent ARCA and several rarer entities have been described during the past fifteen years such as ataxia with oculomotor apraxia type 1 (AOA1) and type 2 (AOA2), ataxia with vitamin E deficiency (AVED) and autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The ACAR are characterized by both allelic and non-allelic genetic heterogeneity. They may be divided into three groups: spino-cerebellar ataxia with pure sensory neuropathy; cerebellar ataxia with sensori-motor axonal neuropathy; pure cerebellar ataxia (i.e. ataxia of purely cerebellar origin that may be associated with other symptoms). Common physiological pathways are involved in several ARCA, such as DNA repair deficiency (AOA1, ataxia telangiectasia [AT]…), RNA termination disorder (AOA2), mitochondrial defect (FRDA, sensory ataxic neuropathy with dysarthria and ophthalmoplegia [Sando]…), lipoprotein assembly defects (AVED, abetalipoproteinemia [ABL]), chaperon protein disorders (ARSACS, Marinesco-Sjögren syndrome [MSS]) or peroxysomal diseases (Refsum disease [RD]).
New nanotechnology methods and high throughput gene analysis as well as bioinformatics should lead to the identification of several new ARCAs in the next few years despite the rarity of these entities. However, the challenge of the next decades will be the discovery of efficient treatments for these disabling neurodegenerative disorders.
Clinicians should be aware of the more frequent ARCAs, especially FRDA, in addition to ARCAs for which treatment is available (FRDA, AVED, ABL and RD for instance).
常染色体隐性遗传性小脑共济失调（ARCA）是一类异质性且复杂的遗传性神经退行性疾病，可累及小脑和/或脊髓小脑束、脊髓后柱及周围神经。小脑共济失调通常较为突出，且大多与多种神经或神经外体征相关，导致患者在30岁前出现严重残疾。
弗里德赖希共济失调（FRDA）显然是最常见的ARCA，在过去15年中还发现了一些较为罕见的类型，如1型动眼神经失用性共济失调（AOA1）和2型动眼神经失用性共济失调（AOA2）、维生素E缺乏性共济失调（AVED）以及魁北克-萨格奈常染色体隐性痉挛性共济失调（ARSACS）。ARCA具有等位基因和非等位基因遗传异质性的特点。它们可分为三组：伴有纯感觉性神经病变的脊髓小脑共济失调；伴有感觉运动性轴索性神经病变的小脑共济失调；纯小脑共济失调（即纯粹起源于小脑的共济失调，可能伴有其他症状）。几种ARCA涉及共同的生理途径，如DNA修复缺陷（AOA1、共济失调毛细血管扩张症[AT]等）、RNA终止障碍（AOA2）、线粒体缺陷（FRDA、伴有构音障碍和眼肌麻痹的感觉性共济失调性神经病变[Sando]等）、脂蛋白组装缺陷（AVED、无β脂蛋白血症[ABL]）、伴侣蛋白疾病（ARSACS、马里内斯科-施约格伦综合征[MSS]）或过氧化物酶体疾病（雷夫叙姆病[RD]）。
尽管这些疾病较为罕见，但新的纳米技术方法、高通量基因分析以及生物信息学在未来几年应能促使发现几种新的ARCA。然而，未来几十年的挑战将是找到针对这些致残性神经退行性疾病的有效治疗方法。
临床医生应了解更常见的ARCA，尤其是FRDA，此外还应了解有可用治疗方法的ARCA（例如FRDA、AVED、ABL和RD）。
