{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T12:00:48Z","timestamp":1792411248794,"version":"4.4.0"},"reference-count":78,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HD091142"],"award-info":[{"award-number":["1R01HD091142"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Succinic semialdehyde dehydrogenase deficiency (SSADHD) is an inherited metabolic disorder characterized by an accumulation of \u03b3\u2010aminobutyric (GABA). In addition to its synaptic role as an inhibitory neurotransmitter, GABA also plays an important role in myelination. We aimed to investigate the relationship between GABA and myelination abnormalities in SSADHD patients and the mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Brain MRIs performed on 44 individuals (23 with SSADHD and 21 healthy controls) were independently reviewed by two neuroradiologists and scored using a disease\u2010specific myelination scoring system. Inter\u2010rater reliability (IRR) was assessed by the intraclass correlation coefficient. Myelination scores of SSADHD individuals were correlated with clinical, biochemical, magnetic resonance spectroscopy, and genetic data. Additionally, we investigated the expression of myelin\u2010related genes in a mouse SSADHD model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Dysmyelination in SSADHD patients was overall mild, but significantly greater than in healthy controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). In SSADHD patients, lower myelination scores were significantly correlated with younger age (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.775,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and higher plasma GABA (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u2009\u22120.722,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and \u03b3\u2010hydroxybutyric acid (GHB) (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u2009\u22120.683,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001). In SSADH\u2010deficient mice, there was reduced expression of genes encoding myelin basic protein (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), myelin\u2010associated oligodendrocyte basic protein (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), and mitochondrial aspartate transporter (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Excessive GABA and GHB, which characterize SSADHD and are further pronounced in younger SSADHD individuals, may account for delayed oligodendrocyte maturation and altered myelination dynamics in this disorder. Studying the properties of dysmyelination in this unique disorder enhances our understanding of GABA's mediating role on myelination and may contribute to monitoring disease progression and managing other white\u2010matter neurological disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>NCT03758521<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70148","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T12:04:25Z","timestamp":1753963465000},"page":"2193-2205","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Central Dysmyelination in SSADH\u2010Deficient Humans and Mice"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3132-1379","authenticated-orcid":false,"given":"Itay","family":"Tokatly Latzer","sequence":"first","affiliation":[{"name":"Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"School of Medicine, Faculty of Medical and Health Sciences Tel\u2010Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4975-7330","authenticated-orcid":false,"given":"Henry H. C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Rosamund Stone Zander Translational Neuroscience Center Boston Children's Hospital  Boston Massachusetts USA"},{"name":"F.M. Kirby Neurobiology Center Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Radiology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2337-9928","authenticated-orcid":false,"given":"Mariarita","family":"Bertoldi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlyn","family":"Fung","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"F.M. Kirby Neurobiology Center Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Medical Microbiology &amp; Immunology Department University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer V.","family":"Steele","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"F.M. Kirby Neurobiology Center Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Department of Neuroscience DePauw University  Greencastle Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eren","family":"Kule","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"F.M. Kirby Neurobiology Center Boston Children's Hospital  Boston Massachusetts USA"},{"name":"School of Medicine Ko\u00e7 University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijie","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"F.M. Kirby Neurobiology Center Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6495-5928","authenticated-orcid":false,"given":"Alexander","family":"Rotenberg","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"F.M. Kirby Neurobiology Center Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0040-7540","authenticated-orcid":false,"given":"Jean\u2010Baptiste","family":"Roullet","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy College of Pharmacy and Pharmaceutical Sciences, Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6373-1068","authenticated-orcid":false,"given":"Phillip L.","family":"Pearl","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10288"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2020.04.004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010730"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng727"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12668"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000048603"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1405468"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2016.06.009"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.01.006"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181b163a5"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052606"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-023-02613-6"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12635"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12668"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17592"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12723"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073821993000"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073821991295"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10629"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000059549.70717.80"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2024.108363"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2019.07.014"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00256"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(98)00016-1"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04255.x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23093"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-021-00693-w"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-008-0941-7"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24585"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0247-6"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.12.008"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073820987742"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-020-00550-1"},{"issue":"9","key":"e_1_2_9_35_1","first-page":"1761","article-title":"Adrenoleukodystrophy: A Scoring Method for Brain MR Observations","volume":"15","author":"Loes D. J.","year":"1994","journal-title":"American Journal of Neuroradiology"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2003-41276"},{"issue":"6","key":"e_1_2_9_37_1","first-page":"1099","article-title":"Concepts of Myelin and Myelination in Neuroradiology","volume":"21","author":"Barkovich A. J.","year":"2000","journal-title":"American Journal of Neuroradiology"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.04.058"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A2542"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2565-1_15"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/bms.1200190207"},{"key":"e_1_2_9_42_1","doi-asserted-by":"crossref","unstructured":"A.Peek T.Rebbeck A.Leaver et\u00a0al. \u201cA Comprehensive Guide to Mega\u2010Press for Gaba Measurement \u201d(2021) medRxiv. 2021.11.24.21266827.","DOI":"10.1101\/2021.11.24.21266827"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.26706"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24566"},{"key":"e_1_2_9_45_1","unstructured":"S. W.Provencher \u201cLCModel & LCMgui User's Manual Version 6.3\u20101R \u201d(2021) [February 2023] http:\/\/s\u2010provencher.com\/pub\/LCModel\/manual\/manual.pdf."},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.40"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab314"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl190"},{"key":"e_1_2_9_49_1","unstructured":"\u201cConSurf Web Sever \u201d (2019) [January 2025] https:\/\/consurf.tau.ac.il\/."},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2016.11.022"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-024-09538-9"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcm.2016.02.012"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2024.02.010"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000213485"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20960"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018529323734"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0155317"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20080"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.07.003"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-2254(200005\/06)2:3<165::AID-JGM107>3.0.CO;2-R"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-018-0480-6"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.04-02-00561.1984"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490310104"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1991.tb00817.x"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858411403317"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200811071"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01163-w"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bht309"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.115.100594"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5635-03.2004"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23489"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24262"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.807911"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhn238"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3990"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae029"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv209"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A3483"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0236-y"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.70148","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T07:04:32Z","timestamp":1763449472000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.70148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":78,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/acn3.70148"],"URL":"https:\/\/doi.org\/10.1002\/acn3.70148","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,31]]},"assertion":[{"value":"2025-04-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}