Abstract
Background
Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder that affects 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 confirmation via gene sequencing. Novel mutations affecting protein function were predicted with Mutation-Taster, PolyPhen-2, CADD and SIFT software. 3D models of the mutated proteins were generated 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.
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Acknowledgments
The authors want to thank all patients and their families for their assistance and support. We express our thanks to all those colleagues involved in patient care.
Funding
This work was supported by Grants from the National Key Research and Development Program of China (2016YFC0905100).
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WHS contributed to the conception and design, collection and assembly of data, data analysis and interpretation, and drafting/revising the manuscript. YQW, YMW, and XRD contributed to in silico analysis. BBW, WL, PZ, YPZ, BY, MZ, and HJW contributed to provision of study materials or patients. WHZ contributed to the conception, design, and the administrative support. All authors approved the final manuscript as submitted.
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This study was approved by the ethics committee of Children’s Hospital, Fudan University. Informed consent for publication was obtained from all of the families of individual participants included in the study.
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Sun, WH., Wu, BB., Wang, YQ. et al. Identification of eight novel mutations in 11 Chinese patients with maple syrup urine disease. World J Pediatr 16, 401–410 (2020). https://doi.org/10.1007/s12519-020-00349-1
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DOI: https://doi.org/10.1007/s12519-020-00349-1