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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.
We describe a 37-year-old patient who first walked at 23 months. Aged seven, he had cerebellar ataxia and brisk reflexes in all limbs. Cognitive function has been normal but ataxia and spasticity have progressed. He also developed epilepsy, myoclonus and …
Contributors JCS wrote the initial manuscript and contributed to the analysis and interpretation of data. SMM, ID, RP, GA, SN, FB, PG and MMR contributed to drafting and rewriting the initial manuscript as well as to the analysis and interpretation of data. All authors give approval for publication. PG and MMR contributed equally to this manuscript.
Funding This work was supported by the National Institutes of Neurological Diseases and Stroke and office of Rare Diseases, Grant number U54NS065712 (to SMM, MMR), Ataxia UK (SN, PG) the Medical Research Council and the Muscular Dystrophy Campaign (MMR).
Competing interests SMM has received support for her research from the National Institutes of Neurological Diseases and Stroke and office of Rare Diseases (U54NS065712). SN has received research grant funding from Ataxia UK. PG has received research grant funding from Ataxia UK. MMR serves on the editorial boards of the Journal of Neurology, Neurosurgery and Psychiatry, Neuromuscular Disorders and the Journal of the Peripheral Nervous System and on the editorial advisory board of Brain. MMR is grateful to the Medical Research Council (MRC) and the National Institutes of Neurological Diseases and Stroke and office of Rare Diseases (U54NS065712) for their support. This work was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme.
Provenance and peer review Not commissioned; externally peer reviewed.