{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:12:58Z","timestamp":1793052778049,"version":"4.5.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2000,7,1]],"date-time":"2000-07-01T00:00:00Z","timestamp":962409600000},"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":[[2000,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurological dysfunction is common in patients with maple syrup urine disease (MSUD). However, the mechanisms underlying the neuropathology of this disorder are poorly understood. We determined the concentrations of all amino acids in plasma of patients with MSUD during crises (with severe CNS symptoms) and after recovery in the hope of detecting possible alterations of these levels during metabolic decompensation. Blood samples obtained from 11 children with MSUD aged 1 month to 7 years and from 10 age\u2010matched controls (5 months to 6 years) with no evidence of metabolic disease were examined for their amino acid content by high\u2010performance liquid chromatography. We observed that leucine, isoleucine and valine concentrations were respectively 30, 9 and 3 times higher than normal values, whereas the concentrations of the large neutral amino acids (LNAA) phenylalanine, tyrosine, tryptophan and methionine were significantly lower during metabolic decompensation as compared to the controls. In addition, concentrations of leucine, but not of valine or isoleucine, were inversely related to the LNAA concentrations in plasma. The concentrations of these amino acids in plasma returned to normal values when patients were clinically well. CSF amino acid concentrations also showed decreased amounts of LNAA and increased concentrations of branched\u2010chain amino acids. It is possible that the decrease in plasma concentrations of LNAA may lead to a deficit of these essential amino acids in the brain as well as of their products such as proteins and neurotransmitters, a fact that might be related to the neurological dysfunction of MSUD.<\/jats:p>","DOI":"10.1023\/a:1005668431926","type":"journal-article","created":{"date-parts":[[2002,12,21]],"date-time":"2002-12-21T23:07:17Z","timestamp":1040512037000},"page":"505-512","source":"Crossref","is-referenced-by-count":55,"title":["Reduction of large neutral amino acid concentrations in plasma and CSF of patients with maple syrup urine disease during crises"],"prefix":"10.1002","volume":"23","author":[{"given":"M.","family":"Wajner","sequence":"first","affiliation":[{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre RS Brazil"},{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas de Sa\u00fade, UFRGS  Porto Alegre, RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. M.","family":"Coelho","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. G.","family":"Barschak","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. R.","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre RS Brazil"},{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas de Sa\u00fade, UFRGS  Porto Alegre, RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. F.","family":"Pires","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre RS Brazil"},{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas de Sa\u00fade, UFRGS  Porto Alegre, RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. L. G.","family":"Lulhier","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. R.","family":"Vargas","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre RS Brazil"},{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas de Sa\u00fade, UFRGS  Porto Alegre, RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2000,7]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2164-0947.1966.tb02252.x"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/121.5.663"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108201"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01800722"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2360929"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1990.70.1.43"},{"key":"e_1_2_1_8_1","first-page":"1239","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Chuang DT","year":"1995"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00441705"},{"key":"e_1_2_1_10_1","first-page":"671","volume-title":"The Metabolic Basis of Inherited Disease","author":"Danner DJ","year":"1989"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196505202722006"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000243858"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0600095"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1978.tb10489.x"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-197305000-00003"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-113-28456"},{"key":"e_1_2_1_17_1","first-page":"13","volume-title":"HPL C of Small Peptides","author":"Joseph MH","year":"1986"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1976.tb04457.x-i1"},{"key":"e_1_2_1_19_1","first-page":"235","article-title":"Comparative aspects of the apparent Michaelis constant for neutral amino acid transport in several animal tissues","volume":"84","author":"Lerner J","year":"1986","journal-title":"Comp Biochem Physiol"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1968.tb06202.x"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)75327-7"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64031252.x"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.34.4.454"},{"key":"e_1_2_1_24_1","first-page":"393","article-title":"Inhibition of brain\u2010glutamic decarboxylase by phenylalanine, valine, and leucine derivatives: a suggestion concerning the etiology of the neurological defect in phenylketonuria and branched\u2010chain ketonuria","volume":"10","author":"Tashian RE","year":"1961","journal-title":"Metabolism"},{"key":"e_1_2_1_25_1","first-page":"78","article-title":"Valine entry into rat brain after diet\u2010induced changes in plasma amino acids","volume":"252","author":"Tews JK","year":"1987","journal-title":"Am J Physiol"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(91)90153-N"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1971.tb06996.x"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.80.6.579"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/1357-2725(96)00019-2"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1023%2FA%3A1005668431926","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1023\/A%3A1005668431926","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T20:22:55Z","timestamp":1694809375000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1023\/A%3A1005668431926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,7]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2000,7]]}},"alternative-id":["10.1023\/A:1005668431926"],"URL":"https:\/\/doi.org\/10.1023\/a:1005668431926","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,7]]}}}