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  • Hereditary leukoencephalopathy with axonal spheroids: a spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series

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Neurogenetics
Research paper
Hereditary leukoencephalopathy with axonal spheroids: a spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series
  1. David S Lynch1,2,
  2. Zane Jaunmuktane3,
  3. Una-Marie Sheerin1,
  4. Rahul Phadke3,
  5. Sebastian Brandner3,
  6. Ionnis Milonas4,
  7. Andrew Dean5,
  8. Nin Bajaj6,
  9. Nuala McNicholas7,
  10. Daniel Costello7,
  11. Simon Cronin7,
  12. Chris McGuigan8,
  13. Martin Rossor9,
  14. Nick Fox9,
  15. Elaine Murphy10,
  16. Jeremy Chataway10,
  17. Henry Houlden1,11
  1. 1Department of Molecular Neuroscience, The National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, Queen Square, London, UK
  2. 2The Leonard Wolfson Experimental Neurology Centre, The National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London UK
  3. 3Division of Neuropathology and Department of Neurodegenerative Disease, The National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, Queen Square, London, UK
  4. 4Aristotle University of Thessaloniki, Thessaloniki, Greece
  5. 5Department of Neuropathology, Addenbrooke's Hospital, Cambridge, UK
  6. 6Department of Neurology, Queens Medical Centre, Nottingham, UK
  7. 7Department of Neurology, Cork University Hospital, Wilton, Cork, Ireland
  8. 8University College Dublin, St. Vincent's University Hospital, Dublin, Ireland
  9. 9Department of Neurodegeneration, Dementia Research Centre, London, UK
  10. 10Department of Neuroinflammation, The National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, Queen Square, London, UK
  11. 11Neurogenetics Laboratory, The National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, Queen Square, London, UK
  1. Correspondence to Dr David S Lynch, Department of Molecular Neuroscience, The National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; david.lynch.13{at}ucl.ac.uk

Abstract

Background Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a hereditary, adult onset leukodystrophy which is characterised by the presence of axonal loss, axonal spheroids and variably present pigmented macrophages on pathological examination. It most frequently presents in adulthood with dementia and personality change. HDLS has recently been found to be caused by mutations in the colony stimulating factor-1 receptor (CSF1R) gene.

Methods In this study, we sequenced the CSF1R gene in a cohort of 48 patients from the UK, Greece and Ireland with adult onset leukodystrophy of unknown cause.

Results Five pathogenic mutations were found, including three novel mutations. The presentations ranged from suspected central nervous system (CNS) vasculitis to extrapyramidal to cognitive phenotypes. The case histories and imaging are presented here, in addition to neuropathological findings from two cases with novel mutations.

Conclusion We estimate that CSF1R mutations account for 10% of idiopathic adult onset leukodystrophies and that genetic testing for CSF1R mutations is essential in adult patients presenting with undefined CNS vasculitis or a leukodystrophy with prominent neuropsychiatric signs or dementia.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/jnnp-2015-310788

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