Article

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-Sjogren 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).
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Langue : FRANCAIS