{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T01:48:47Z","timestamp":1791856127171,"version":"4.3.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key R&D Program of Zhejiang","award":["2024C03151"],"award-info":[{"award-number":["2024C03151"]}]},{"name":"Key R&D Program of Zhejiang","award":["2023C03027"],"award-info":[{"award-number":["2023C03027"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000030"],"award-info":[{"award-number":["82000030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31872724"],"award-info":[{"award-number":["31872724"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Program on Key Basic Research Project","award":["2022YFC2703401"],"award-info":[{"award-number":["2022YFC2703401"]}]},{"name":"Special Fund for the Incubation of Young Clinical Scientist"},{"name":"The Children's Hospital of Zhejiang University School of Medicine","award":["CHZJU2022YS005"],"award-info":[{"award-number":["CHZJU2022YS005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder originating from defects in the branched-chain \u03b1-ketoacid dehydrogenase (BCKDH) complex encoded by BCKDHA, BCKDHB and DBT. This condition presents a spectrum of symptoms and potentially fatal outcomes. Although numerous mutations in the BCKDH complex genes associated with MSUD have been identified, the relationship between specific genotypes remains to be fully elucidated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>Our objective was to predict the pathogenicity of these genetic mutations and establish potential links between genotypic alterations and the clinical phenotypes of MSUD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Retrospective population-based cohort.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We analyzed 20 MSUD patients from the Children\u2019s Hospital at Zhejiang University School of Medicine (Hangzhou, China), recorded from January 2010 to December 2023. Patients\u2019 blood samples were collected by heel-stick through neonatal screening, and amino acid profiles were measured by tandem mass spectrometry. In silico methods were employed to assess the pathogenicity, stability and biophysical properties. Various computation tools were utilized for assessment, namely PredictSNP, MAGPIE, iStable, Align GVGD, ConSurf and SNP effect.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We detected 25 distinct mutations, including 12 novel mutations. The BCKDHB gene was the most commonly affected (53.3%) compared to the BCKDHA gene (20.0%) and DBT gene (26.7%). In silico webservers predicted all novel mutations were disease-causing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study highlights the genetic complexity of MSUD and underscores the importance of early detection and intervention. Integrating neonatal screening with advanced sequencing methodologies is pivotal in ensuring precise diagnosis and effective management of MSUD, thereby significantly improving the prognosis for individuals afflicted with this condition.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/qjmed\/hcae104","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T19:37:11Z","timestamp":1717616231000},"page":"717-727","source":"Crossref","is-referenced-by-count":5,"title":["Genotypic and phenotypic spectrum of maple syrup urine disease in Zhejiang of China"],"prefix":"10.1093","volume":"117","author":[{"given":"X","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital of Zhejiang University, School of Medicine, National Clinical Research Center for Child Health , 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Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital of Zhejiang University, School of Medicine, National Clinical Research Center for Child Health , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital of Zhejiang University, School of Medicine, National Clinical Research Center for Child Health , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital of Zhejiang University, School of Medicine, National Clinical Research Center for Child Health , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital of Zhejiang University, School of Medicine, National Clinical Research Center for Child Health , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital of Zhejiang University, School of Medicine, National Clinical Research Center for Child Health , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Children\u2019s Hospital of Zhejiang University, School of Medicine, National Clinical Research Center for Child Health , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital of Zhejiang University, School of Medicine, National Clinical Research Center for Child Health , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital of Zhejiang University, School of Medicine, National Clinical Research Center for Child Health , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital of Zhejiang University, School of Medicine, National Clinical Research Center for Child Health , 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