{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:07:39Z","timestamp":1791220059473,"version":"4.1.0"},"reference-count":8,"publisher":"BMJ","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2011,6,14]]},"published-print":{"date-parts":[[2011,10]]},"abstract":"\n Background<\/jats:title>\n Leukoencephalopathy with brain stem and spinal cord involvement and brain lactate elevation (LBSL) was recently shown to be caused by mutations in the DARS2<\/jats:italic> gene, encoding a mitochondrial aspartyl-tRNA synthetase. So far, affected individuals were invariably compound heterozygous for two mutations in DARS2<\/jats:italic>, and drug treatments have remained elusive.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Prospective 2-year follow-up of the natural history of the main presenting symptoms in a homozygous DARS2<\/jats:italic> mutation carrier, followed by a 60 day treatment with acetazolamide in two different doses and with two random treatment interruptions.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The patient presented with exercise-induced paroxysmal gait ataxia and areflexia as an atypical phenotype associated with a novel homozygous DARS2<\/jats:italic> mutation. These features showed an excellent dose-dependent, sustained treatment response to a carbonic anhydrase inhibitor. Pathogenic mutations in episodic ataxia genes were excluded, thus making it highly unlikely that this phenotype was because of episodic ataxia as a second disorder besides LBSL.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This case demonstrates that DARS2<\/jats:italic> mutation homozygosity is not lethal, as suggested earlier, but compatible with a rather benign disease course. More importantly, it extends the phenotypic spectrum of LBSL and reveals that at least some DARS2<\/jats:italic>-associated phenotypic features might be readily treatable. However, future observations of paroxsymal ataxia and, possibly, areflexia in other DARS2<\/jats:italic>-mutated patients are warranted to further corroborate our finding that DARS2<\/jats:italic> mutations can lead to a paroxsymal ataxia phenotype.<\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/jmg.2011.090282","type":"journal-article","created":{"date-parts":[[2011,7,12]],"date-time":"2011-07-12T20:35:55Z","timestamp":1310502955000},"page":"713-715","source":"Crossref","is-referenced-by-count":48,"title":["Acetazolamide-responsive exercise-induced episodic ataxia associated with a novel homozygous DARS2<\/i> mutation: Figure 1"],"prefix":"10.1136","volume":"48","author":[{"given":"Matthis","family":"Synofzik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Schicks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Lindig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Biskup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Hansel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Lehmann-Horn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludger","family":"Sch\u00f6ls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2011,7,11]]},"reference":[{"key":"2025101713515839000_48.10.713.1","unstructured":"Van der Knaap MS Scheper GC . Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. In: Pagon RA Bird TC Dolan CR , eds. GeneReviews [Internet]. Seattle (WA): University of Washington, 2010."},{"key":"2025101713515839000_48.10.713.2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2013"},{"key":"2025101713515839000_48.10.713.3","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000219042.60538.92"},{"key":"2025101713515839000_48.10.713.4","doi-asserted-by":"publisher","DOI":"10.1159\/000102171"},{"key":"2025101713515839000_48.10.713.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2008.06.002"},{"key":"2025101713515839000_48.10.713.6","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.068221"},{"key":"2025101713515839000_48.10.713.7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802134200"},{"key":"2025101713515839000_48.10.713.8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0743h.x"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.2011.090282","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T20:52:09Z","timestamp":1760734329000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.2011.090282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,7,11]]},"references-count":8,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2011,9,19]]},"published-print":{"date-parts":[[2011,10]]}},"alternative-id":["10.1136\/jmg.2011.090282"],"URL":"https:\/\/doi.org\/10.1136\/jmg.2011.090282","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,7,11]]}}}