{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:36:44Z","timestamp":1772818604926,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T00:00:00Z","timestamp":1543795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Boston Intellectual and Development Disabilities Research Center","award":["5U54HD090255"],"award-info":[{"award-number":["5U54HD090255"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Succinic Semialdehyde Dehydrogenase (SSADH) deficiency is a disorder of elevated gamma\u2010amino butyric acid (<jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>) and gamma hydroxybutyric acid (<jats:styled-content style=\"fixed-case\">GHB<\/jats:styled-content>) and a complex neuropsychiatric profile. Adult reports suggest worsening epilepsy and high <jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content> risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Subjects with confirmed <jats:styled-content style=\"fixed-case\">SSADH<\/jats:styled-content> deficiency were recruited into a longitudinal study. Plasma thyroid hormone and total <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">GHB<\/jats:styled-content> were quantified by standard clinical chemistry methodologies and mass spectrometry, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 133 subjects with <jats:styled-content style=\"fixed-case\">SSADH<\/jats:styled-content> deficiency are enrolled in the registry; 49 participated in the longitudinal study. The age range of the population is 8\u00a0weeks to 63\u00a0years (median 7.75\u00a0year; 44% male). There is a significant difference in proportions among the age groups in subjects affected with hypotonia, compulsive behavior, sleep disturbances, and seizures. Epilepsy is present in 50% of the total population, and more prevalent in subjects 12\u00a0years and older (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.001).\u00a0The median age of onset for absence seizures was 2\u00a0years, and 12\u00a0years for generalized tonic\u2010clonic seizures (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). The <jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content> rate in adults was 12% (4\/33). There was a significant age\u2010dependent negative correlation between <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content> and T<jats:sub>3<\/jats:sub> levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>There is an age\u2010dependent association with worsening of epilepsy, behavioral disturbances including obsessive\u2010compulsive behavior, and sleep disturbances with age in <jats:styled-content style=\"fixed-case\">SSADH<\/jats:styled-content> deficiency. There is a high risk of <jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content>. We have observed more absence seizures in younger patients, compared to tonic\u2010clonic in the older cohort, which correlates with age\u2010related changes in <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">GHB<\/jats:styled-content> concentration and thyroid function, as well as the natural history of seizures in the murine model.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.696","type":"journal-article","created":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T05:05:13Z","timestamp":1543899913000},"page":"114-120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Age\u2010related phenotype and biomarker changes in <scp>SSADH<\/scp> deficiency"],"prefix":"10.1002","volume":"6","author":[{"given":"Melissa L.","family":"DiBacco","sequence":"first","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Baptiste","family":"Roullet","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kush","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madalyn N.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana C.","family":"Walters","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. Michael","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip L.","family":"Pearl","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,12,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10629"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000059549.70717.80"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2005.09.012"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(03)00113-6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001906"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-9980-7"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2017_3"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2004.09.008"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.02.131"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20686"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9499-5"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181b163a5"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31825dcf71"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2013.09.007"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2006.01.033"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2006.tb01313.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1997.tb07414.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1034-y"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2014.01.003"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00229-9"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.14581\/jer.17015"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(03)00107-4"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facn3.696","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.696","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T20:51:59Z","timestamp":1694724719000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,3]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1002\/acn3.696"],"URL":"https:\/\/doi.org\/10.1002\/acn3.696","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,3]]},"assertion":[{"value":"2018-10-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}