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The ARSACS phenotype can include supranuclear gaze palsy and skin lipofuscin deposits
  1. James C Stevens1,2,
  2. Sinéad M Murphy3,
  3. Indran Davagnanam4,5,
  4. Rahul Phadke6,
  5. Glenn Anderson6,
  6. Suran Nethisinghe1,2,
  7. Fion Bremner7,
  8. Paola Giunti1,2,
  9. Mary M Reilly1,2
  1. 1MRC Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK
  2. 2Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
  3. 3Department of Neurology, The Adelaide and Meath Hospital Dublin, Incorporating the National Children's Hospital, Tallaght, Dublin, Ireland
  4. 4Department of Neuroradiology, National Hospital for Neurology and Neurosurgery and Institute of Neurology, London, UK
  5. 5Department of Brain Repair and Rehabilitation, National Hospital for Neurology and Neurosurgery, London, UK
  6. 6Department of Neuropathology, The National Hospital for Neurology and Neurosurgery, London, UK
  7. 7Department of Neuro-ophthalmology, The National Hospital for Neurology and Neurosurgery, London, UK
  1. Correspondence to Dr James Stevens, Consultant Neurologist, North Bristol NHS Trust, Frenchay Hospital, Bristol BS16 7DT, UK; james.stevens{at}

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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 al6 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 al7 detected a deletion of SACS combined with a hemizygous SACS mutation causing early-onset ARSACS with hearing impairment.

Case report

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 …

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