Introduction

The autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) phenotype was first characterised in patients from Quebec, all of whom had young onset spasticity and gait ataxia. Other features included distal amyotrophy, extensor plantar responses, cerebellar speech, saccadic intrusion in smooth pursuit and hypermyelinated retinal nerve fibres.1 Seven percent had seizures. Spasticity and ataxia were progressive. Electromyography showed denervation. Nerve conduction studies showed reduced conduction velocities with absent sensory action potentials. Nerve biopsy showed a lack of large myelinated axons.2 Subsequent analysis of this cohort has shown two founder mutations in the SACS gene—c.6594delT and c.5254C>T.3

Identification of mutations in SACS as the cause of ARSACS facilitated the detection of further cases worldwide, revealing greater phenotypic variation. Vermeer et al screened 43 patients presenting with ataxia prior to age 25 (suggesting an autosomal recessive cause4), finding 16 patients with SACS mutations.5 One patient had onset aged 12, two showed dystonia. Baets et al 6 screened 85 patients with at least two of cerebellar ataxia, spasticity and peripheral neuropathy, finding 18 different mutations. In five of these patients, disease onset was at over 20 years, one patient had no signs of peripheral neuropathy, several patients presented primarily with peripheral neuropathy and only one had hypermyelinated retinal nerve fibres using standard fundoscopy. Two patients had mild cognitive impairment and one epilepsy. Breckpot et al 7 detected a deletion of SACS combined with a hemizygous SACS mutation causing early-onset ARSACS with hearing impairment.