{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:26:43Z","timestamp":1789522003294,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,2,5]],"date-time":"2015-02-05T00:00:00Z","timestamp":1423094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Valine, leucine, and isoleucine are essential branched chain amino acids (BCAAs). When BCAA metabolism is genetically impaired in human, serum levels of BCAA and\/or their metabolites rise considerably, causing severe neurological dysfunction. The first step in BCAA catabolism is catalyzed by branched chain aminotransferase (BCAT). Hypervalinemia and hyperleucine\u2010isoleucinemia caused by <jats:italic>BCAT<\/jats:italic> gene mutation in human have not been reported previously. A 25\u2010year\u2010old man presented with headache complaints and mild memory impairment for about six years. Brain MRI showed symmetric white matter abnormal signals. Metabolic studies revealed remarkably elevated plasma valine and leucine concentrations. Maple syrup urine disease (MSUD) diagnosis was not supported since all genes for the branched\u2010chain \u03b1\u2010keto acid dehydrogenase complex (BCKD) gene were normal. Interestingly, two heterogeneous <jats:italic>BCAT2<\/jats:italic> gene mutations were found in the patient, including c.509G\u2009&gt;\u2009A (p.Arg170Gln) and c.790G\u2009&gt;\u2009A (p.Glu264Lys). In addition, c.509G\u2009&gt;\u2009A (p.Arg170Gln) and c.790G\u2009&gt;\u2009A (p.Glu264Lys) were found in his father and mother, respectively, suggesting an autosomal recessive disorder. BCAT2 functional studies demonstrated that the two <jats:italic>BCAT2<\/jats:italic> gene mutations resulted in decreased BCAT2 enzyme activity. After treatment with vitamin B6, the levels of BCAA, especially valine were remarkably decreased and brain MRI lesions were improved. These findings suggest a new type of branched chain amino acid metabolism disorder. This rare case provides great insight into the further understanding of BCAA metabolism and its defect in human. <jats:italic>BCAT2<\/jats:italic> gene mutations can cause hypervalinemia and hyperleucine\u2010isoleucinemia, which are associated with brain white matter lesions.<\/jats:p>","DOI":"10.1007\/s10545-015-9814-z","type":"journal-article","created":{"date-parts":[[2015,2,4]],"date-time":"2015-02-04T08:27:29Z","timestamp":1423038449000},"page":"855-861","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Hypervalinemia and hyperleucine\u2010isoleucinemia caused by mutations in the branched\u2010chain\u2010amino\u2010acid aminotransferase gene"],"prefix":"10.1002","volume":"38","author":[{"given":"X. L.","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University 45 Changchun Street Beijing 100053 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. J.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University 45 Changchun Street Beijing 100053 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University 45 Changchun Street Beijing 100053 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. H.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Xuanwu Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P.","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University 45 Changchun Street Beijing 100053 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2008.12.005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/136.1.207S"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/41.1.62"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi020200i"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-9639(03)00051-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.9.4982"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2006.05.007"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12044"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/135.6.1557S"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-003-0955-7"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-013-0255-5"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.01.016"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2003.09.010"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-003-0039-3"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00276.2003"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/136.1.324S"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.87.322"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.81.46"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI19574"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199709)21:1<92::AID-GLIA10>3.0.CO;2-W"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-015-9814-z","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T04:49:21Z","timestamp":1694753361000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-015-9814-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,5]]},"references-count":20,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1007\/s10545-015-9814-z"],"URL":"https:\/\/doi.org\/10.1007\/s10545-015-9814-z","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,5]]}}}