Spinocerebellar ataxias (SCAs) are a group of progressive and irreversible neurological diseases affecting gait and movement coordination.  Many result from cerebellar degeneration or the impairment of a portion of the neuroaxis that contributes to cerebellar inflow or outflow.  Spinocerebellar ataxia with axonal neuropathy (SCAN1) is characterized by late-childhood-onset, recessive ataxia with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, and pes cavus and stepagge gait.  All affected individuals have normal intelligence.  Diagnosis of SCAN1 is based on clinical findings, family history, MRI, and nerve conduction studies.

The mechanism underlying the pathogenesis of SCAN1 revolves around the role played by TDP1 in repairing chromosomal single-strand breaks arising independently of DNA replication from abortive topoisomerase-1 activity or oxidative stress.  In normal cells, TDP1 is part of multiprotein single-strand break repair (SSBR) complexes; however these complexes become catalytically inactive in SCAN1 cells.  Defective SSBR is thought to disrupt the maintenance of genetic integrity in postmitotic neurons leading to SCAN1.