{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:25:19Z","timestamp":1789521919545,"version":"build-2803163510"},"reference-count":80,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,2,3]],"date-time":"2011-02-03T00:00:00Z","timestamp":1296691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Disorders of branched\u2010chain amino\/keto acid metabolism encompass diverse entities, including maple syrup urine disease (MSUD), the \u2018classical\u2019 organic acidurias isovaleric acidemia (IVA), propionic acidemia (PA), methylmalonic acidemia (MMA) and, among others, rarely described disorders such as 2\u2010methylbutyryl\u2010CoA dehydrogenase deficiency (MBDD) or isobutyryl\u2010CoA dehydrogenase deficiency (IBDD). Our focus in this review is to highlight the biochemical basis underlying recent advances and ongoing challenges of long\u2010term conservative therapy including precursor\/protein restriction, replenishment of deficient substrates, and the use of antioxidants and anaplerotic agents which refill the Krebs cycle. Ongoing clinical assessments of affected individuals in conjunction with monitoring of disease\u2010specific biochemical parameters remain essential. It is likely that mass spectrometry\u2010based \u2018metabolomics\u2019 may be a helpful tool in the future for studying complete biochemical profiles and diverse metabolic phenotypes. Prospective studies are needed to test the effectiveness of adjunct therapies such as antioxidants, ornithine\u2010alpha\u2010ketoglutarate (OKG) or creatine in addition to specialized diets and to optimize current therapeutic strategies in affected individuals. With the individual life\u2010time risk and degree of severity being unknown in asymptomatic individuals with MBDD or IBDD, instructions regarding risks for metabolic stress and fasting avoidance along with clinical monitoring are reasonable interventions at the current time. Overall, it is apparent that carefully designed prospective clinical investigations and multicenter cohort\u2010controlled trials are needed in order to leverage that knowledge into significant breakthroughs in treatment strategies and appropriate approaches.<\/jats:p>","DOI":"10.1007\/s10545-010-9269-1","type":"journal-article","created":{"date-parts":[[2011,2,2]],"date-time":"2011-02-02T14:38:01Z","timestamp":1296657481000},"page":"29-40","source":"Crossref","is-referenced-by-count":68,"title":["Advances and challenges in the treatment of branched\u2010chain amino\/keto acid metabolic defects"],"prefix":"10.1002","volume":"35","author":[{"given":"Ina","family":"Knerr","sequence":"first","affiliation":[{"name":"Children's and Adolescents\u2019 Hospital, Otto\u2010Heubner Centrum, Pediatric Metabolic Unit Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Germany"},{"name":"Otto\u2010Heubner\u2010Centrum f\u00fcr Kinder\u2010 und Jugendmedizin, P\u00e4diatrische Stoffwechselmedizin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Campus Virchow\u2010Klinikum, Augustenburger Platz 1 Berlin D\u201013353 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Weinhold","sequence":"additional","affiliation":[{"name":"Children's and Adolescents\u2019 Hospital, Otto\u2010Heubner Centrum, Pediatric Metabolic Unit Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Vockley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Michael","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Michigan Technological University Houghton MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,2,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0182-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.04.014"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.02.018"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp595"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.08.028"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-007-9077-y"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2008.12.005"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3046.2006.00569.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0320-1"},{"key":"e_1_2_7_11_1","unstructured":"Brunetti\u2010PierriN LanpherB ErezA AnanievaEA IslamM MariniJC SunQ YuC HegdeM LiJ WynnRM ChuangDT HutsonS LeeB(2010)Phenylbutyrate therapy for maple syrup urine disease.Hum Mol Genet Nov 23[Epub ahead of print]"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(01)00130-9"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2010.008"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520801912128"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-121848"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","unstructured":"ChandlerRJ ChandrasekaranS Carrillo\u2010CarrascoN SenacJS HofherrS BarryMA VendittiCP(2010)Adeno\u2010associated virus serotype 8 (AAV8) gene transfer rescues a neonatal lethal murine model of propionic acidemia.Hum Gene Ther Oct 15[Epub ahead of print]","DOI":"10.1089\/hum.2010.164"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/134.10.2858S"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e3181a7c270"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30090"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0278-z"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem.2010.082"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2009.07.005"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200006000-00025"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(00)24252-3"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.05.103"},{"key":"e_1_2_7_26_1","first-page":"7","article-title":"Production and characterization of murine models of classic and intermediate maple syrup urine disease","volume":"31","author":"Homanics GE","year":"2006","journal-title":"BMC Med Genet"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1189-6"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.11.5.1919"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-1947-1-98"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1726-4901(09)70408-3"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000074972.36356.89"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0415-8"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1071-6"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2005.048421"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)32718-2"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.112.1.74"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9066-x"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.08.119"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.06.007"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105467200"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.109.6.999"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9444-4"},{"key":"e_1_2_7_43_1","first-page":"CD006659","article-title":"Carnitine supplementation for inborn errors of metabolism","volume":"15","author":"Nasser M","year":"2009","journal-title":"Cochrane Database Syst Res Apr"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1053\/siny.2001.0087"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31802f78d6"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2010.01.002"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9423-9"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.01.005"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21107"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.1998.2758"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.09.002"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:BOLI.0000045798.12425.1b"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1053\/siny.2001.0083"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2008.05.447"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1197-6"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.03.003"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-009-0356-2"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2004.03.006"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20060221"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0276-1"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.08.006"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.99"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715760802311179"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1126-8"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109879"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2005.01209.x"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.12.007"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj080362"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0351-7"},{"key":"e_1_2_7_70_1","first-page":"12","article-title":"2\u2010methylbutyryl\u2010CoA dehydrogenase deficiency in Hmong infants identified by expanded newborn screen","volume":"106","author":"Van Calcar SC","year":"2007","journal-title":"WMJ"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30089"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:BOLI.0000037353.13085.e2"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12603-010-0109-7"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2007.089011"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI19574"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2445"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2003.08.012"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0267-2"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-0205"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp024"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-008-0804-2"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-010-9269-1","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1007\/s10545-010-9269-1","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-010-9269-1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T22:28:49Z","timestamp":1694816929000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-010-9269-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2,3]]},"references-count":80,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,1]]}},"alternative-id":["10.1007\/s10545-010-9269-1"],"URL":"https:\/\/doi.org\/10.1007\/s10545-010-9269-1","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2,3]]}}}