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Pathophysiology and Treatment of Canavan Disease

  • David Pleasure
  • Fuzheng Guo
  • Olga Chechneva
  • Peter Bannerman
  • Jennifer McDonough
  • Travis Burns
  • Yan Wang
  • Vanessa Hull
Original Paper
  • 31 Downloads

Canavan Disease

Canavan disease is a recessively inherited vacuolar leukodystrophy caused by ASPA mutations [1, 2, 3]. ASPA encodes aspartoacylase, an oligodendroglial enzyme required for cleavage of the abundant brain amino acid N-acetyl-l-aspartate (NAA) to acetate and l-aspartate [4]. ASPA mutations are relatively common in Ashkenazi Jews, with carrier frequency estimates ranging between 1:40 and 1:60, but also occur, though substantially less often, in many other human populations [3, 5, 6]. The disease classically presents in infancy with ataxia, hypotonia, and failure to acquire normal developmental milestones, often in association with macrocephaly and seizures [3]. In atypical cases in which some aspartoacylase enzymatic activity remains, disease onset is delayed until several years after birth [2, 7, 8]. Neuroimaging shows brain white matter signal abnormalities, and, at later time-points, ventricular enlargement [9, 10]. In vivo proton nuclear magnetic resonance spectroscopy...

Keywords

Canavan disease Aspartoacylase (encoded by ASPA) N-acetyltransferase 8-like (encoded by Nat8l) NaDC3 (encoded by Slc13a3) Vacuolar (“spongiform”) leukodystrophy N-acetyl-l-aspartate (NAA) Gene therapy 

Notes

Acknowledgements

This study was supported by Shriners Hospitals Grant 439043; NIH 1R21NS096004-01; and the Dana Foundation.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute for Pediatric Regenerative ResearchShriners Hospitals for Children Northern California and UC Davis School of MedicineSacramentoUSA
  2. 2.Department of Biological Sciences, School of Biomedical SciencesKent State UniversityKentUSA
  3. 3.SacramentoUSA

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