{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:48:20Z","timestamp":1791978500242,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T00:00:00Z","timestamp":1548720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008731","name":"Association Europ\u00e9enne contre les Leucodystrophies","doi-asserted-by":"publisher","award":["ELA 2009\u2010007I4"],"award-info":[{"award-number":["ELA 2009\u2010007I4"]}],"id":[{"id":"10.13039\/501100008731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM108911"],"award-info":[{"award-number":["R01 GM108911"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008731","name":"Association Europ\u00e9enne contre les Leucodystrophies","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      <jats:italic>SLC13A3<\/jats:italic>\n                      encodes the plasma membrane Na\n                      <jats:sup>+<\/jats:sup>\n                      \/dicarboxylate cotransporter 3, which imports inside the cell 4 to 6 carbon dicarboxylates as well as N\u2010acetylaspartate (NAA). SLC13A3 is mainly expressed in kidney, in astrocytes, and in the choroid plexus. We describe two unrelated patients presenting with acute, reversible (and recurrent in one) neurological deterioration during a febrile illness. Both patients exhibited a reversible leukoencephalopathy and a urinary excretion of \u03b1\u2010ketoglutarate (\u03b1KG) that was markedly increased and persisted over time. In one patient, increased concentrations of cerebrospinal fluid NAA and dicarboxylates (including \u03b1KG) were observed. Extensive workup was unsuccessful, and a genetic cause was suspected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole exome sequencing (WES) was performed. Our teams were connected through GeneMatcher.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WES analysis revealed variants in\n                      <jats:italic>SLC13A3<\/jats:italic>\n                      . A homozygous missense mutation (p.Ala254Asp) was found in the first patient. The second patient was heterozygous for another missense mutation (p.Gly548Ser) and an intronic mutation affecting splicing as demonstrated by reverse transcriptase polymerase chain reaction performed in muscle tissue (c.1016 + 3A &gt; G). Mutations and segregation were confirmed by Sanger sequencing. Functional studies performed on HEK293T cells transiently transfected with wild\u2010type and mutant SLC13A3 indicated that the missense mutations caused a marked reduction in the capacity to transport \u03b1KG, succinate, and NAA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      SLC13A3 deficiency causes acute and reversible leukoencephalopathy with marked accumulation of \u03b1KG. Urine organic acids (especially \u03b1KG and NAA) and\n                      <jats:italic>SLC13A3<\/jats:italic>\n                      mutations should be screened in patients presenting with unexplained reversible leukoencephalopathy, for which SLC13A3 deficiency is a novel differential diagnosis.\n                      <jats:bold>ANN NEUROL 2019;85:385\u2013395.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25412","type":"journal-article","created":{"date-parts":[[2019,1,12]],"date-time":"2019-01-12T00:01:19Z","timestamp":1547251279000},"page":"385-395","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["<i>SLC13A3<\/i>\n                    variants cause acute reversible leukoencephalopathy and \u03b1\u2010ketoglutarate accumulation"],"prefix":"10.1002","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7223-2706","authenticated-orcid":false,"given":"Joseph P.","family":"Dewulf","sequence":"first","affiliation":[{"name":"Laboratory of Physiological Chemistry, de Duve Institute Universit\u00e9 catholique de Louvain  Brussels Belgium"},{"name":"Walloon Excellence in Life Sciences and Biotechnology (WELBIO)  Brussels Belgium"},{"name":"Department of Laboratory Medicine, Cliniques universitaires Saint\u2010Luc Universit\u00e9 catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Wiame","sequence":"additional","affiliation":[{"name":"Laboratory of Physiological Chemistry, de Duve Institute Universit\u00e9 catholique de Louvain  Brussels Belgium"},{"name":"Walloon Excellence in Life Sciences and Biotechnology (WELBIO)  Brussels 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