Vol.:(0123456789) 1 3 World Journal of Pediatrics https://doi.org/10.1007/s12519-020-00349-1 ORIGINAL ARTICLE Identifcation of eight novel mutations in 11 Chinese patients with maple syrup urine disease Wei‑Hua Sun 1  · Bing‑Bing Wu 1,2  · Ya‑Qiong Wang 1  · Meng‑Yuan Wu 1  · Xin‑Ran Dong 1  · Yue‑Ping Zhang 4  · Wei Lu 3  · Ping Zhang 1  · Bin Yang 6  · Min Zhang 7  · Hong‑Jiang Wu 1  · Wen‑Hao Zhou 1,2,5 Received: 24 July 2019 / Accepted: 18 February 2020 © Children’s Hospital, Zhejiang University School of Medicine 2020 Abstract Background Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder that afects the degradation of branched-chain amino acids and is associated with acute and chronic brain dysfunction. This study presents 11 new patients with MSUD and describes the clinical characteristics and gene mutations reported in Chinese individuals. Methods During 2011–2018, 11 pedaitric patients with MSUD from 11 Chinese families were analyzed based on clinical characteristics and mass spectrometry, with confrmation via gene sequencing. Novel mutations afecting protein function were predicted with Mutation-Taster, PolyPhen-2, CADD and SIFT software. 3D models of the mutated proteins were gener- ated by using the SWISS-MODEL online server, and the models were visualized in PyMOL. The characteristics and gene mutations in patients with MSUD were analyzed retrospectively. Results Seventeen mutations in the BCKDHA, BCKDHB and DBT genes were found, 8 of which are novel: c.55C>/T, c.349C>T, c.565C>T, c.808G>A, c.859C>G, and c.1270dupC in BCKDHA; c.275-2A>G in BCKDHB; and c.1291C>T in DBT. Eight patients died. Two patients had severe mental retardation and were physically handicapped. One patient with the intermediate type had relatively good prognosis, with mild psychomotor retardation and adiposity. Four mothers underwent amniocentesis for prenatal diagnosis during their second pregnancy; two fetuses were wild type, and two were carriers of one heterozygous mutation. Conclusions Eight novel mutations were associated with MSUD in Chinese patients. Prenatal diagnosis was successfully performed by genetic analysis. Mutations in the BCKDHB gene were found in the majority of Chinese patients with MSUD. Keywords Branched-chain amino acids · Maple syrup urine disease · Mutation · Prenatal diagnosis * Wen-Hao Zhou zhouwenhao@fudan.edu.cn 1 Institute of Pediatrics, Shanghai Key Laboratory of Birth Defects, Children’s Hospital of Fudan University, Wanyuan Road 399, Shanghai 201102, China 2 Key Laboratory of Neonatal Diseases, Ministry of Health, Children’s Hospital of Fudan University, Shanghai 201102, China 3 Department of Endocrinology, Children’s Hospital of Fudan University, Shanghai 201102, China 4 Shanghai Ji-ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China 5 Shanghai Key Laboratory of Birth Defects, The Translational Medicine Center of Children Development and Disease of Fudan University, Children’s Hospital of Fudan University, Shanghai 201102, China 6 Department of Radiology, Children’s Hospital of Shanghai, Shanghai 201102, China 7 Department of Neurology, Children’s Hospital of Fudan University, Shanghai 201102, China