{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:22:20Z","timestamp":1747149740804,"version":"3.40.5"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM008683"],"award-info":[{"award-number":["T32 GM008683"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Type II D\u20102\u2010Hydroxyglutaric aciduria (T2D2HGA) is caused by a gain\u2010of\u2010function pathogenic variant in Isocitrate Dehydrogenase 2 (IDH2). Patients with T2D2HGA commonly present with developmental delay, seizures, cardiomyopathy, and arrhythmias. The recently approved IDH2\u2010inhibitor Enasidenib targets the p.Arg140Gln pathogenic <jats:italic>IDH2<\/jats:italic> variant and decreases production of D2HGA. We present a 7\u2010year\u2010old female with T2D2HGA due to the p.Arg140Gln variant. She was diagnosed at 3\u2010years\u2010old after presenting with global developmental delay, leukoencephalopathy, communicating hydrocephalus, seizures, and dilated cardiomyopathy. At age 3\u2009years 11\u2009months, 50\u2009mg Enasidenib daily was initiated. Primary outcomes included seizure frequency, hospital admissions, development, and cardiac structure. Laboratories were monitored biweekly for common Enasidenib side effects. Our patient tolerated Enasidenib well. Urine 2\u2010HGA decreased significantly from 244\u2009mg\/g creatinine to undetectable within 2\u2009weeks of treatment. Inpatient admissions decreased from 8 during the 2\u2009years preceding treatment to 1 during treatment. She has been seizure\u2010free since Enasidenib initiation. Echocardiography showed improvement in dilated cardiomyopathy with normal left ventricular systolic function. Developmental assessment demonstrated improvements in gross motor, fine motor, language, and socialization domains. Treatment was complicated by mild elevations in alanine transaminase (118\u2009IU\/L, range 0\u201328) and creatine kinase (334\u2009U\/L, range 45\u2013198) that resolved by decreasing Enasidenib dosing frequency to three times weekly. Enasidenib is a viable treatment for Type II D2HGA with benefits including developmental gains, fewer acute medical interventions, and cardiomyopathy improvement. While drug\u2010induced hepatitis is a novel adverse effect of Enasidenib, it can be ameliorated by decreasing dose frequency.<\/jats:p>","DOI":"10.1002\/jmd2.12421","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T05:40:05Z","timestamp":1713332405000},"page":"156-162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Enasidenib\u2010induced hepatitis in an individual with Type II D2\u2010hydroxyglutaric aciduria"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6210-4214","authenticated-orcid":false,"given":"Jessica I.","family":"Gold","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Northwell Health  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianna K.","family":"Stefanatos","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry and Behavioral Sciences Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie L.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Prenatal Pediatrics Institute Children's National Hospital  Washington DC USA"},{"name":"The George Washington University School of Medicine and Health Sciences  Washington DC USA"},{"name":"Division of Fetal and Translational Medicine Children's National Hospital  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adeline","family":"Vanderver","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Neurology Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanmati","family":"Cuddapah","sequence":"additional","affiliation":[{"name":"Section of Biochemical Genetics, Division of Genetics, Department of Pediatrics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010662\u201049771\u20105"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1192632"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010006\u20100317\u20109"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010012\u20109462\u20105"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/aian.AIAN_231_20"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2008.01.003"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201004\u2010779405"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201004\u2010779447"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010023\u201002382\u20109"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1005548005393"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010017\u20100813\u20102"},{"key":"e_1_2_12_13_1","unstructured":"Enasidenib for the treatment of relapsed or refractory acute myeloid leukemia patients with an IDH2 mutation. 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