A novel SACS mutation in an atypical case with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an inherited neurodegenerative disorder with symptoms of spastic ataxia, neuropathy, pyramidal sign, finger and foot deformities, and hypermyelination of retinal nerve fibers. SACS is mutated in ARSACS. The clinical diversity of ARSACS is recognized, which sometimes makes its diagnosis difficult. By using homozygosity mapping, we identified a novel homozygous c.12020C > T missense mutation in a consanguineous Japanese family with atypical clinical features. In addition to the absence of spasticity and hypermyelinated retinal nerve fibers, the present case had urinary dysfunction, impotence, and severe constipation, indicating the possibility of autonomic dysfunction. Furthermore, we showed the diagnostic usefulness of MRI even for the case of atypical clinical features. It had been considered that cases without obvious spasticity were very rare, however recent reports on atypical cases as well as our case indicate that ARSACS cases without obvious spasticity might be more frequent than previously thought. We should be aware of atypical features of ARSACS for the correct diagnosis.