Pathophysiology and Treatment of Canavan Disease
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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 . 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 . 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...
KeywordsCanavan 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
This study was supported by Shriners Hospitals Grant 439043; NIH 1R21NS096004-01; and the Dana Foundation.
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