{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T20:05:37Z","timestamp":1760645137204},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T00:00:00Z","timestamp":1133395200000},"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":[[2005,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>To evaluate the significance of inborn metabolic disorders of the pyrimidine degradation pathway, 450 children with unspecific neurological symptoms were comprehensively studied; 200 healthy children were recruited as controls. Uracil and thymine as well as their degradation products in urine were determined with an improved method based on reversed\u2010phase HPLC coupled with electrospray ionization tandem mass spectrometry and detection by multiple\u2010reaction monitoring using stable\u2010isotope\u2010labelled reference compounds as internal standards.<\/jats:p><jats:p>From the results of the control group we established age\u2010related reference ranges of all pyrimidine degradation products. In the patient group, two children with dihydropyrimidine dehydrogenase (DPYD) deficiency were identified; one of these was homozygous for the exon 14\u2010skipping mutation of the <jats:italic>DPYD<\/jats:italic> gene. In addition, two patients with high uracil, dihydrouracil and \u03b2\u2010ureidopropionate were found to have ornithine transcarbamylase deficiency. In the urine of 9 patients, \u03b2\u2010alanine was markedly elevated owing to treatment with vigabatrin, an irreversible inhibitor of GABA transaminase, which interferes with \u03b2\u2010alanine breakdown. Four patients had exclusively high levels of \u03b2\u2010aminoisobutyrate (\u03b2\u2010AIB) due to a low activity of the <jats:sc>D<\/jats:sc>\u2010\u03b2\u2010AIB\u2010pyruvate aminotransferase, probably without clinical significance.<\/jats:p><jats:p>In conclusion, quantitative investigation of pyrimidine metabolites in children with unexplained neurological symptoms, particularly epileptic seizures with or without psychomotor retardation, can be recommended as a helpful tool for diagnosis in clinical practice. Sensitive methods and age\u2010related reference ranges enable the detection of partial enzyme deficiencies.<\/jats:p>","DOI":"10.1007\/s10545-005-0133-7","type":"journal-article","created":{"date-parts":[[2006,1,25]],"date-time":"2006-01-25T09:35:29Z","timestamp":1138181729000},"page":"1109-1122","source":"Crossref","is-referenced-by-count":19,"title":["Comprehensive analysis of pyrimidine metabolism in 450 children with unspecific neurological symptoms using high\u2013pressure liquid chromatography\u2013electrospray ionization tandem mass spectrometry"],"prefix":"10.1002","volume":"28","author":[{"given":"C.","family":"Schmidt","sequence":"first","affiliation":[{"name":"Division of Metabolic and Endocrine Diseases University Children's Hospital Heidelberg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U.","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer\u2010Bosch Institute of Clinical Pharmacology Stuttgart Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Kohlm\u00fcller","sequence":"additional","affiliation":[{"name":"Division of Metabolic and Endocrine Diseases University Children's Hospital Heidelberg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"M\u00fcrdter","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer\u2010Bosch Institute of Clinical Pharmacology Stuttgart Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U. M.","family":"Zanger","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer\u2010Bosch Institute of Clinical Pharmacology Stuttgart Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Schwab","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer\u2010Bosch Institute of Clinical Pharmacology Stuttgart Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. F.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Division of Metabolic and Endocrine Diseases University Children's Hospital Heidelberg"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-200x.2000.01274.x"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005374426168"},{"issue":"2","key":"e_1_2_1_4_1","first-page":"1","article-title":"Presumptive ureidopropionase deficiency as a new defect in pyrimidine catabolism found with in vitro H\u2010NMR spectroscopy","volume":"21","author":"Assmann B","year":"1998","journal-title":"J Inherit Metab Dis"},{"issue":"1","key":"e_1_2_1_5_1","first-page":"237","article-title":"Ureidopropionase deficiency\u2014a new case presenting with febrile status epilepticus","volume":"27","author":"Assmann B","year":"2004","journal-title":"J Inherit Metab Dis"},{"issue":"2","key":"e_1_2_1_6_1","first-page":"130","article-title":"Diagnosis of dihydropyrimidine dehydrogenase deficiency in neonate with thymine\u2010uraciluria","volume":"9","author":"Au KM","year":"2003","journal-title":"Hong Kong Med J"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(84)90206-7"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005332606213"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(00)86037-5"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/109065703322146777"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.426"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/46.4.445"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-0232(03)00044-8"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.354"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02435991"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005356806329"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/0-306-46843-3_47"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/0-306-46843-3_49"},{"issue":"5","key":"e_1_2_1_19_1","first-page":"1149","article-title":"Lethal outcome of a patient with a complete dihydropyrimidine dehydrogenase deficiency after administration of 5\u2010fluorouracil: frequency of the common IVS14+1G>A mutation causing DPD deficiency","volume":"7","author":"Kuilenburg AB","year":"2001","journal-title":"Clin Cancer Res"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/46.12.1916"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/45.4.539"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-005-0133-7","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-005-0133-7","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T02:15:22Z","timestamp":1694744122000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-005-0133-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,12]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2005,12]]}},"alternative-id":["10.1007\/s10545-005-0133-7"],"URL":"https:\/\/doi.org\/10.1007\/s10545-005-0133-7","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,12]]}}}