{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:12:31Z","timestamp":1792552351450,"version":"4.5.0"},"reference-count":9,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["K01ES025435"],"award-info":[{"award-number":["K01ES025435"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Child Neurology Open"],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:p>Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a progressive disorder associated with deficiency of mitochondrial aspartyl-tRNA synthetase, a homodimer encoded by the gene DARS2. There is a wide range in age of onset of symptoms, typically from childhood to adulthood, with very few cases of infantile onset disease reported. We report a child at age 10 years with perinatal onset of symptoms evidenced by congenital microcephaly with progression to severe but non-lethal epileptic encephalopathy and spastic quadriplegia. A comprehensive epilepsy focused gene panel performed as a trio with parents detected a novel homozygous DARS2 variant. This variant is located at the dimer interface in a critical catalytic domain and is expected to result in markedly reduced enzyme activity which likely explains the severe and early onset symptoms in this case.<\/jats:p>","DOI":"10.1177\/2329048x211019173","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T05:12:18Z","timestamp":1621919538000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Perinatal Manifestations of\n                    <i>DARS2<\/i>\n                    -Associated Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation (LBSL)"],"prefix":"10.1177","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1979-3931","authenticated-orcid":false,"given":"Julie","family":"Ngo","sequence":"first","affiliation":[{"name":"Michigan State University College of Human Medicine, Grand Rapids, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy W.","family":"Prokop","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University College of Human Medicine, Grand Rapids, MI, USA"},{"name":"Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Umfleet","sequence":"additional","affiliation":[{"name":"Spectrum Health Helen Devos Children\u2019s Hospital Grand Rapids, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9136-101X","authenticated-orcid":false,"given":"Laurie H.","family":"Seaver","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University College of Human Medicine, Grand Rapids, MI, USA"},{"name":"Spectrum Health Helen Devos Children\u2019s Hospital Grand Rapids, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,5,25]]},"reference":[{"key":"bibr1-2329048X211019173","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121564"},{"key":"bibr2-2329048X211019173","doi-asserted-by":"publisher","DOI":"10.1159\/000362448"},{"key":"bibr3-2329048X211019173","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-017-3258-3"},{"key":"bibr4-2329048X211019173","doi-asserted-by":"publisher","DOI":"10.1038\/ng2013"},{"key":"bibr5-2329048X211019173","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2011.090282"},{"key":"bibr6-2329048X211019173","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2012.05.007"},{"key":"bibr7-2329048X211019173","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcp.2015.06.005"},{"key":"bibr8-2329048X211019173","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2017.03.006"},{"key":"bibr9-2329048X211019173","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1329395"}],"container-title":["Child Neurology Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/2329048X211019173","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/2329048X211019173","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/2329048X211019173","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:58:06Z","timestamp":1777391886000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/2329048X211019173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,1]]},"references-count":9,"alternative-id":["10.1177\/2329048X211019173"],"URL":"https:\/\/doi.org\/10.1177\/2329048x211019173","relation":{},"ISSN":["2329-048X","2329-048X"],"issn-type":[{"value":"2329-048X","type":"print"},{"value":"2329-048X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,1]]},"article-number":"2329048X211019173"}}