{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:28:05Z","timestamp":1792081685373,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,9,24]],"date-time":"2014-09-24T00:00:00Z","timestamp":1411516800000},"content-version":"vor","delay-in-days":54,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatrics International"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\n                    anavan disease (\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    ) is a genetic neurodegenerative leukodystrophy that results in the spongy degeneration of white matter in the brain.\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    is characterized by mutations in the gene encoding aspartoacylase (\n                    <jats:styled-content style=\"fixed-case\">ASPA<\/jats:styled-content>\n                    ), the substrate enzyme that hydrolyzes\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\n                    <\/jats:italic>\n                    \u2010acetylaspartic acid (\n                    <jats:styled-content style=\"fixed-case\">NAA<\/jats:styled-content>\n                    ) to acetate and aspartate. Elevated\n                    <jats:styled-content style=\"fixed-case\">NAA<\/jats:styled-content>\n                    and subsequent deficiency in acetate associated with this disease cause progressive neurological symptoms, such as macrocephaly, visuocognitive dysfunction, and psychomotor delay. The prevalence of\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    is higher among Ashkenazi Jewish people, and several types of mutations have been reported in the gene coding\n                    <jats:styled-content style=\"fixed-case\">ASPA<\/jats:styled-content>\n                    . Highly elevated\n                    <jats:styled-content style=\"fixed-case\">NAA<\/jats:styled-content>\n                    is more specific to\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    than other leukodystrophies, and an examination of urinary\n                    <jats:styled-content style=\"fixed-case\">NAA<\/jats:styled-content>\n                    concentration is useful for diagnosing\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    . Many researchers are now examining the mechanisms responsible for white matter degeneration or dysmyelination in\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    using mouse models, and several persuasive hypotheses have been suggested for the pathophysiology of\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    . One is that\n                    <jats:styled-content style=\"fixed-case\">NAA<\/jats:styled-content>\n                    serves as a water pump; consequently, a disorder in\n                    <jats:styled-content style=\"fixed-case\">NAA<\/jats:styled-content>\n                    catabolism leads to astrocytic edema. Another hypothesis is that the hydrolyzation of\n                    <jats:styled-content style=\"fixed-case\">NAA<\/jats:styled-content>\n                    in oligodendrocytes is essential for myelin synthesis through the supply of acetate. Although there is currently no curative therapy for\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    , dietary supplements are candidates that may retard the progression of the symptoms associated with\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    . Furthermore, gene therapies using viral vectors have been investigated using rat models. These therapies have been found to be tolerable with no severe long\u2010term adverse effects, reduce the elevated\n                    <jats:styled-content style=\"fixed-case\">NAA<\/jats:styled-content>\n                    in the brain, and may be applied to humans in the future.\n                  <\/jats:p>","DOI":"10.1111\/ped.12422","type":"journal-article","created":{"date-parts":[[2014,6,30]],"date-time":"2014-06-30T22:53:07Z","timestamp":1404168787000},"page":"477-483","source":"Crossref","is-referenced-by-count":82,"title":["<scp>C<\/scp>\n                    anavan disease: Clinical features and recent advances in research"],"prefix":"10.1111","volume":"56","author":[{"given":"Hideki","family":"Hoshino","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Tokyo  Tokyo Japan"},{"name":"Division of Neurology National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Kubota","sequence":"additional","affiliation":[{"name":"Division of Neurology National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.74.1907.71"},{"key":"e_1_2_11_3_1","first-page":"682","article-title":"[Demyelinizing diseases in man and animals: Remarks and conclusions]","volume":"54","author":"Bertrand I","year":"1954","journal-title":"Acta Neurol. 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