Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a form originally identified in families originating in the Quebec region of Charlevoix-Saguenay 20 years ago. Patients with this condition have since been identified in Tunisia. In this disorder progressive gait unsteadiness, slurred speech and limb spasticity, followed by distal amyotrophy begins at age 3-20 years, although patients never walk normally. Fundoscopic examination reveals a unique diagnostic finding, myelinated fibers embedding retinal blood vessels. There is ankle arreflexia and knee hyperreflexia. Nystagmus, Babinski signs, and proprioceptive sensory loss are universally present. Some patients have amyotrophy of the lower limbs. Echocardiograms frequently show mitral valve prolapse, but no cardiomyopathy. Patients are confined to a wheelchair by the fifth decade. Recently the gene responsible for ARSACS was identified on chromosome 13q11-12, and the protein designated sacsin. Sacsin contains three large segments with sequence similarity to each other, and that are highly evolutionarily conserved.