[Autosomal recessive cerebellar ataxias]

Abstract

Introduction: 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.

State of art: 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]).

Perspectives: 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.

Conclusion: 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).