{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T01:53:32Z","timestamp":1775786012860,"version":"3.50.1"},"reference-count":11,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["5\/7\/1658\/CH\/Adhoc\/2019\u2010RBMCH"],"award-info":[{"award-number":["5\/7\/1658\/CH\/Adhoc\/2019\u2010RBMCH"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epileptic Disorders"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Arginase deficiency, which leads to hyperargininaemia is a rare urea cycle disorder caused by a mutation in the ARG1 gene. It is an under\u2010recognized cause of pediatric developmental epileptic encephalopathy, with the key coexistent clinical features being developmental delay or regression and spasticity. Detection of ARG1 gene mutation on genetic testing is the confirmatory diagnostic test. However, elevated levels of plasma arginine and low plasma arginase level can be considered as biochemical markers for diagnosis. We present two cases of arginase deficiency with genetically confirmed ARG1 mutation in one and biochemical confirmation in both. As the spectrum of epilepsy in arginase deficiency has been less explored, we attempted to elucidate the novel electroclinical features and syndromic presentations in these patients. Informed consent was obtained from families of patients. Electroclinical diagnosis was consistent with Lennox Gastaut syndrome (LGS) in the first patient while the second patient had refractory atonic seizures with electrophysiological features consistent with developmental and epileptic encephalopathy. Though primary hyperammonaemia is not a consistent feature, secondary hyperammonaemia in the setting of infectious triggers and drugs like valproate (valproate sensitivity) has been well described as also observed in our patient. In the absence of an overt antecedent in a child with spasticity and seizure disorder, with a progressive course consistent with a developmental epileptic encephalopathy, arginase deficiency merits consideration. Diagnosis often has important therapeutic implications with respect to dietary management and choice of the appropriate antiseizure medications.<\/jats:p>","DOI":"10.1002\/epd2.20081","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T07:54:09Z","timestamp":1685174049000},"page":"556-561","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Arginase deficiency\u2014An unheralded cause of developmental epileptic encephalopathy"],"prefix":"10.1002","volume":"25","author":[{"given":"Harini","family":"Pavuluri","sequence":"first","affiliation":[{"name":"R Madhavan Nayar Centre for Comprehensive Epilepsy Care Sree Chitra Tirunal Institute for Medical Sciences &amp; Technology  Thiruvananthapuram India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manna","family":"Jose","sequence":"additional","affiliation":[{"name":"R Madhavan Nayar Centre for Comprehensive Epilepsy Care Sree Chitra Tirunal Institute for Medical Sciences &amp; Technology  Thiruvananthapuram India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfiya","family":"Fasaludeen","sequence":"additional","affiliation":[{"name":"R Madhavan Nayar Centre for Comprehensive Epilepsy Care Sree Chitra Tirunal Institute for Medical Sciences &amp; Technology  Thiruvananthapuram India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumya","family":"Sundaram","sequence":"additional","affiliation":[{"name":"R Madhavan Nayar Centre for Comprehensive Epilepsy Care Sree Chitra Tirunal Institute for Medical Sciences &amp; Technology  Thiruvananthapuram India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8564-8436","authenticated-orcid":false,"given":"Ashalatha","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"R Madhavan Nayar Centre for Comprehensive Epilepsy Care Sree Chitra Tirunal Institute for Medical Sciences &amp; Technology  Thiruvananthapuram India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moinak","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Rajiv Gandhi Centre for Biotechnology  Thiruvananthapuram India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-3307","authenticated-orcid":false,"given":"Ramshekhar N.","family":"Menon","sequence":"additional","affiliation":[{"name":"R Madhavan Nayar Centre for Comprehensive Epilepsy Care Sree Chitra Tirunal Institute for Medical Sciences &amp; Technology  Thiruvananthapuram India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"issue":"1","key":"e_1_2_8_2_1","first-page":"1","article-title":"Arginase deficiency manifesting delayed clinical sequelae and induction of a kidney arginase isozyme","volume":"91","author":"Grody Wayne W","year":"1993","journal-title":"Hum Genet"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109\u2010015\u20101354\u20103"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30091"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.11.004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-015-2032-z"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01799578"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1360479"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2012.03.016"},{"issue":"12","key":"e_1_2_8_10_1","first-page":"764","article-title":"Late diagnosis of congenital argininemia during administration of sodium valproate","volume":"146","author":"Christmann D","year":"1990","journal-title":"Rev Neurol (Paris)"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00438892"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389701200502"}],"container-title":["Epileptic Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epd2.20081","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T16:07:22Z","timestamp":1710778042000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epd2.20081"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,31]]},"references-count":11,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/epd2.20081"],"URL":"https:\/\/doi.org\/10.1002\/epd2.20081","archive":["Portico"],"relation":{},"ISSN":["1294-9361","1950-6945"],"issn-type":[{"value":"1294-9361","type":"print"},{"value":"1950-6945","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,31]]},"assertion":[{"value":"2023-03-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}