Spinocerebellar Ataxia Type 1

Among SCA patients the proportion with SCA1 ranges from 3% in the Japan (0% in Korea and Portugal) to 40% in Russia and South Africa, and is found in about 6% of US SCA patients. SCA1 typically has an age of onset in the third or fourth decade, but severe forms of childhood- or juvenile-onset SCA1 have been documented that are known to be due to the more severely expanded alleles. Initial symptoms are gait unsteadiness, but increasing dysarthria and dysphagia soon follow. The rate of progression in adult-onset SCA1 may vary considerably, with confinement to wheelchair between 3 and 17 years after onset and death from ten to 30 years after onset. Death is often related to respiratory failure due to bulbar involvement. Patients with juvenile-onset disease (whose symptoms appear before age 13 years) have still more severe disease, having more widespread CNS involvement and being fatal before age 16.

SCA1 is caused by an expansion in CAG repeat in the SCA1 gene on 6p23 that leads to an elongated tract of glutamine residues within the protein ataxin-1. Ataxin-1 is a cytoplasmic and nuclear protein of unknown function. The diagnosis of SCA1 is established by the demonstration of expansion in one CAG repeat alleles in the SCA1 locus greater than 38 repeats in an ataxia patient.