Early onset absence epilepsy: 1 in 10 cases is caused by GLUT1 deficiency

Authors

  • Todor Arsov,

    1. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
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  • Saul A. Mullen,

    1. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
    2. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia
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  • John A. Damiano,

    1. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
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  • Kate M. Lawrence,

    1. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
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  • Linda L. Huh,

    1. Division of Neurology, Department of Pediatrics, University of British Columbia, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
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  • Melinda Nolan,

    1. Neurology Department, Starship Hospital, Auckland, New Zealand
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  • Helen Young,

    1. Department of Paediatrics, Royal North Shore Hospital Sydney and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia
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  • Anaïs Thouin,

    1. Institute of Neuroscience, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
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  • Hans-Henrik M. Dahl,

    1. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
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  • Samuel F. Berkovic,

    1. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
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  • Douglas E. Crompton,

    1. James Cook University Hospital, Middlesbrough and Institute of Genetic Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
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  • Lynette G. Sadleir,

    1. Departments of Paediatrics, School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand
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  • Ingrid E. Scheffer

    1. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
    2. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia
    3. Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Melbourne, Victoria, Australia
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Address correspondence to Ingrid E. Scheffer, Melbourne Brain Centre, 245 Burgundy St, Heidelberg, Vic. 3084, Australia. E-mail: scheffer@unimelb.edu.au

Summary

Glucose transporter 1 (GLUT1) deficiency caused by mutations of SLC2A1 is an increasingly recognized cause of genetic generalized epilepsy. We previously reported that >10% (4 of 34) of a cohort with early onset absence epilepsy (EOAE) had GLUT1 deficiency. This study uses a new cohort of 55 patients with EOAE to confirm that finding. Patients with typical absence seizures beginning before 4 years of age were screened for solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) mutations or deletions. All had generalized spike-waves on electroencephalography (EEG). Those with tonic and/or atonic seizures were excluded. Mutations were found in 7 (13%) of 55 cases, including five missense mutations, an in-frame deletion leading to loss of a single amino acid, and a deletion spanning two exons. Over both studies, 11 (12%) of 89 probands with EOAE have GLUT1 deficiency. Given the major treatment and genetic counseling implications, this study confirms that SLC2A1 mutational analysis should be strongly considered in EOAE.

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