{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:56:05Z","timestamp":1792155365221,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Guanidinoacetate methyltransferase (GAMT) deficiency is a rare autosomal recessive creatine biosynthesis disorder. Reports specifically focusing on adult patients remain scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We report a 52\u2010year\u2010old female (the oldest documented case of GAMT deficiency to date) presenting with severe intellectual disability, refractory epilepsy, and adult\u2010onset disease progression. Whole\u2010exome sequencing identified novel compound heterozygous\n                      <jats:italic>GAMT<\/jats:italic>\n                      variants (c.265_267del and c.253G&gt;T), and magnetic resonance spectroscopy confirmed cerebral creatine depletion. Remarkably, initiating oral creatine supplementation at age 52 achieved complete seizure freedom, normalization of the electroencephalogram (EEG), and significant motor function recovery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A comprehensive review revealed that untreated adult patients face a high risk of progressive neurological deterioration. Compared to the pediatric cohort, adults exhibited a significantly higher prevalence of movement disorders (69.2% vs. 33.1%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and a trend toward a higher prevalence of epilepsy (92.3% vs. 74.2%). Especially, atonic seizures (drop attacks) are particularly characteristic of adult GAMT deficiency, with EEGs frequently demonstrating background slowing, multifocal epileptiform discharges, and electrodecremental patterns.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>This study underscores that continuous disease progression and prolonged neurotoxicity still could compromise the well\u2010being of adult GAMT deficiency patients. Accurate diagnosis is essential for adults presenting with developmental and epileptic encephalopathy (DEE) phenotype, as even late treatment for GAMT deficiency can still dramatically alleviate the epileptic burden and reverse motor decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>We report the oldest known adult diagnosed with GAMT deficiency. Our case demonstrates that starting creatine treatment even at age 52 can dramatically reduce seizures and restore motor function. Literature shows that untreated adults suffer from more severe epilepsy and movement disorders than children, with symptoms worsening over time. These findings highlight the critical need for genetic testing in adults with unexplained severe epilepsy; timely creatine supplementation can halt cognitive decline and significantly restore quality of life.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70370","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:28:52Z","timestamp":1792153732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reversal of refractory epilepsy in an adult with\n                    <scp>GAMT<\/scp>\n                    deficiency: A case report and comparative literature review"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7955-2498","authenticated-orcid":false,"given":"Wei\u2010Hung","family":"Sung","sequence":"first","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation Kaohsiung Chang Gung Memorial Hospital  Kaohsiung 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Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4570-5712","authenticated-orcid":false,"given":"Meng\u2010Han","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Neurology Kaohsiung Chang Gung Memorial Hospital  Kaohsiung Taiwan"},{"name":"Postdoctoral Program of Clinical and Experimental Medicine, College of Medicine National Sun Yat\u2010sen University  Kaohsiung Taiwan"},{"name":"School of Medicine, College of Medicine Chang Gung University  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"issue":"2","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/ana.10455","article-title":"Lack of creatine in muscle and brain in an adult with GAMT deficiency","volume":"53","author":"Schulze A","year":"2003","journal-title":"Ann 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