{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T07:40:36Z","timestamp":1776325236228,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI23\/00006"],"award-info":[{"award-number":["PI23\/00006"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/01441"],"award-info":[{"award-number":["PI22\/01441"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epileptic Disorders"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      SLC13A5\u2010developmental and epileptic encephalopathy (SLC13A5\u2010DEE) is a rare autosomal recessive disorder characterized by neonatal\u2010onset seizures, global developmental delay, and amelogenesis imperfecta. Diagnosis can be particularly challenging when genetic testing identifies variants of uncertain significance (VUS). To highlight the diagnostic value of citrate quantification in confirming SLC13A5\u2010DEE. We report a female infant, born to consanguineous parents, who presented with refractory seizures at 14\u2009hours of life. Partial seizure control was initially achieved with oxcarbazepine and lacosamide; however, complete seizure control occurred after the introduction of valproic acid. Brain MRI demonstrated punctate white matter abnormalities. Genetic testing identified a homozygous missense variant in\n                      <jats:italic>SLC13A5<\/jats:italic>\n                      (c.1268G&gt;A, p.Gly423Glu), classified as a VUS. Subsequently, biochemical analysis showed markedly elevated plasma citrate levels (820\u2009\u03bcmol\/L; control values: 19\u201383), and increased urinary citrate excretion (5615\u2009mmol\/mol creatinine; control values: 162\u20132200), consistent with plasmatic membrane Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010coupled citrate transporter dysfunction. The abnormally increased citrate levels supported the reclassification of the variant as likely pathogenic according to ACMG criteria (PP4). At 8\u2009months of age, the patient remained seizure\u2010free but exhibited mild developmental delay. This case underscores the diagnostic value of plasma and urinary citrate quantification as reliable and accessible biomarkers in the diagnostic workup of SLC13A5\u2010DEE. Furthermore, early treatment with valproic acid may improve seizure control and potentially improve developmental outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epd2.70178","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T08:09:42Z","timestamp":1770710982000},"page":"505-511","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The emerging role of citrate as a diagnostic biomarker in\n                    <scp>SLC13A5<\/scp>\n                    \u2010developmental and epileptic encephalopathy"],"prefix":"10.1002","volume":"28","author":[{"given":"Laia","family":"Nou\u2010Fontanet","sequence":"first","affiliation":[{"name":"Early Onset and Genetic Epilepsy Program, Pediatric Neurology Department, Hospital Sant Joan de D\u00e9u University of Barcelona  Barcelona Spain"},{"name":"Complex Epilepsies Research Group Institut de Recerca de Sant Joan de D\u00e9u  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelia","family":"Mu\u00f1oz\u2010Puga","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry Hospital Sant Joan de D\u00e9u University of Barcelona  Barcelona Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Madrigal","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona IDIBAPS (Institut de Investigacions Biom\u00e8diques August Pi I Sunyer)  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Arca","sequence":"additional","affiliation":[{"name":"Neonatology Department, Hospital Cl\u00ednic of Barcelona IDIBAPS  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itziar","family":"Alonso\u2010Colmenero","sequence":"additional","affiliation":[{"name":"Complex Epilepsies Research Group Institut de Recerca de Sant Joan de D\u00e9u  Barcelona Spain"},{"name":"Neurophysiology Program, Pediatric Neurology Department, Hospital Sant Joan de D\u00e9u University of Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Artuch","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry Hospital Sant Joan de D\u00e9u University of Barcelona  Barcelona Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Fons","sequence":"additional","affiliation":[{"name":"Early Onset and Genetic Epilepsy Program, Pediatric Neurology Department, Hospital Sant Joan de D\u00e9u University of Barcelona  Barcelona Spain"},{"name":"Complex Epilepsies Research Group Institut de Recerca de Sant Joan de D\u00e9u  Barcelona Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Madrid 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