Early onset cerebellar ataxia with retained reflexes: a clinical and genetic conundrum.

A taxia is a broad term that literally means " without order ". The term locomotor ataxia has been most commonly used to refer to motor incoordination. The most widely recognized form, cerebellar ataxia (CA), can be classified as primary, idiopathic, acquired (or secondary) and sporadic 1. Primary, CAs are further subdivided into congenital and hereditary, the latter including autosomal recessive (ARCA), autosomal dominant (ADCA) — currently known as spinocerebellar ataxias (SCAs) — X–linked CAs and mitochondrial ataxias 1. Autosomal recessive cerebellar ataxias (ARCA) are part of a large heterogeneous group of hereditary ataxias 2. ARCA are typically characterized by degeneration of the cerebellum and spinal cord and relatively early onset of symptoms (before the age of 20 years). Clinically, impaired gait and balance, motor incoordination, action tremor and dysarthria are almost always present, although other neurological signs and symptoms may be observed 1,2. ARCA include Friedreich's ataxia (FA), considered the commonest form worldwide, and a large group of other rarer genetic disorders, such as the entity defined as early-onset cerebellar ataxia with retained reflexes (EOCARR), which is also known as Harding's ataxia 1,2. FA is estimated to have a prevalence of 2–4/100,000, while ataxia telangiectasia has a prevalence of 1–2.5/100,000, and EOCARR a prevalence of 1/100,000. Other forms of ARCA are much less common 3. In 1981, Harding published a seminal study in which he evaluated 20 patients with EOCARR with a clinical picture characterized by progressive cerebellar ataxia developing within the first two decades of life associated with dysarthria, pyramidal signs and increased knee jerks and upper limb reflexes, probably with autosomal recessive inheritance 2. This nosological entity was later confirmed by other authors, including Filla et al. in Italy and Klockgether et al. in Germany 4,5. EOCARR then became considered a differential diagnosis for FA and its variants such as Friedreich ataxia with retained reflexes (FARR) 1-5. The main point of discussion regarding FA and EOCARR concerns their genetic differences: whereas the genetic cause of FA has been defined (the presence of a GAA triplet repeat expansion in the first intron of the FA gene, on the proximal long arm of chromosome 9), the genetic cause of EOCARR remains unknown, and to date there has only been one study of the condition (in a Tunisian family), in which a locus on chromosome 13q11–12 was identified, but not the causative gene 1,3,6. In this issue of Arquivos de …