{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T22:39:44Z","timestamp":1780353584452,"version":"3.54.1"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["PI12\/02078"],"award-info":[{"award-number":["PI12\/02078"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The first step in branched\u2010chain amino acid (BCAA) catabolism is catalyzed by the two BCAA transferase isoenzymes, cytoplasmic branched\u2010chain amino acid transferase (BCAT) 1, and mitochondrial BCAT2. Defects in the second step of BCAA catabolism cause maple syrup urine disease (MSUD), a condition which has been far more extensively investigated. Here, we studied the consequences of BCAT2 deficiency, an ultra\u2010rare condition in humans. We present genetic, clinical, and functional data in five individuals from four different families with homozygous or compound heterozygous <jats:italic>BCAT2<\/jats:italic> mutations which were all detected following abnormal biochemical profile results or familial mutation segregation studies. We demonstrate that BCAT2 deficiency has a recognizable biochemical profile with raised plasma BCAAs and, in contrast with MSUD, low\u2010normal branched\u2010chain keto acids (BCKAs) with undetectable <jats:sc>l<\/jats:sc>\u2010allo\u2010isoleucine. Interestingly, unlike in MSUD, none of the individuals with BCAT2 deficiency developed acute encephalopathy even with exceptionally high BCAA levels. We observed wide\u2010ranging clinical phenotypes in individuals with BCAT2 deficiency. While one adult was apparently asymptomatic, three individuals had presented with developmental delay and autistic features. We show that the biochemical characteristics of BCAT2 deficiency may be amenable to protein\u2010restricted diet and that early treatment may improve outcome in affected individuals. BCAT2 deficiency is an inborn error of BCAA catabolism. At present, it is unclear whether developmental delay and autism are parts of the variable phenotypic spectrum of this condition or coincidental. Further studies will be required to explore this.<\/jats:p>","DOI":"10.1002\/jimd.12135","type":"journal-article","created":{"date-parts":[[2019,6,9]],"date-time":"2019-06-09T06:30:00Z","timestamp":1560061800000},"page":"809-817","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Expanding the genetic and phenotypic spectrum of branched\u2010chain amino acid transferase 2 deficiency"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4015-0658","authenticated-orcid":false,"given":"Ina","family":"Knerr","sequence":"first","affiliation":[{"name":"National Centre for Inherited Metabolic Disorders Temple Street Children's University Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Colombo","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Faculty of Medicine, Catholic University of the Sacred Heart  Rome Italy"},{"name":"Policlinico Agostino Gemelli  Rome Italy"},{"name":"Center for the Study of Rare Hereditary Diseases Niguarda Ca' Granda Metropolitan Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Urquhart","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust Health Innovation Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Morais","sequence":"additional","affiliation":[{"name":"Centro de Diagnostico de Enfermedades Moleculares, Departamento de Biologia Molecular, Centro de Biologia Molecular Severo Ochoa, Centro de Investigacion Biomedica en Red de Enfermedades Raras Universidad Autonoma de Madrid  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Begona","family":"Merinero","sequence":"additional","affiliation":[{"name":"Centro de Diagnostico de Enfermedades Moleculares, Departamento de Biologia Molecular, Centro de Biologia Molecular Severo Ochoa, Centro de Investigacion Biomedica en Red de Enfermedades Raras Universidad Autonoma de Madrid  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Oyarzabal","sequence":"additional","affiliation":[{"name":"Centro de Diagnostico de Enfermedades Moleculares, Departamento de Biologia Molecular, Centro de Biologia Molecular Severo Ochoa, Centro de Investigacion Biomedica en Red de Enfermedades Raras Universidad Autonoma de Madrid  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Centro de Diagnostico de Enfermedades Moleculares, Departamento de Biologia Molecular, Centro de Biologia Molecular Severo Ochoa, Centro de Investigacion Biomedica en Red de Enfermedades Raras Universidad Autonoma de Madrid  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A.","family":"Jones","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust Health Innovation Manchester  Manchester UK"},{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahat","family":"Perveen","sequence":"additional","affiliation":[{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary A.","family":"Preece","sequence":"additional","affiliation":[{"name":"Children's Hospital Birmingham Women's and Children's NHS Foundation Trust  Birmingham 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University of the Sacred Heart, and Center for Rare Diseases Policlinico Agostino Gemelli  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"MacKinnon","sequence":"additional","affiliation":[{"name":"Structural Genomics Consortium, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangeline","family":"Wassmer","sequence":"additional","affiliation":[{"name":"Children's Hospital Birmingham Women's and Children's NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wyatt W.","family":"Yue","sequence":"additional","affiliation":[{"name":"Structural Genomics Consortium, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Radiology Temple Street Children's 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