Two novel compound heterozygous mutations in the BCKDHB gene that cause the intermittent form of maple syrup urine disease

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• 作者：Yi Guo ; Liu Liming ; Li Jiang
• 关键词：Maple syrup urine disease ; Variant form ; BCKDHB gene ; Mutation
• 刊名：Metabolic Brain Disease
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：30
• 期：6
• 页码：1395-1400
• 全文大小：3,416 KB
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• 作者单位：Yi Guo (1)
  Liu Liming (2)
  Li Jiang (1) (2)
  
  1. Department of Neurology, Children’s Hospital of Chongqing Medical University, Chongqing, China, 400014
  2. Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Neurosciences
  Neurology
  Biochemistry
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7365

文摘

Intermittent maple syrup urine disease (MSUD) is a potentially life-threatening metabolic disorder caused by a deficiency of branched chain α-ketoacid dehydrogenase (BCKD) complex. In contrast to classic MSUD, children with the intermittent form usually have an atypical clinical manifestation. Here, we describe the presenting symptoms and clinical course of a Chinese boy with intermittent MSUD. Mutation analysis identified two previously unreported mutations in exon 7 of the BCKDHB gene: c.767A-gt;?G (p.Y256C) and c.768C-gt;?G (p.Y256X); the parents were each heterozygous for one of these mutations. In silico analysis predicted Y256C probably affects protein structure; Y256X leads to a premature stop codon. This case demonstrates intermittent MSUD should be suspected in cases with symptoms of recurrent encephalopathy, especially ataxia or marked drowsiness, which usually present after the neonatal period and in conjunction with infection. symmetrical basal ganglia damage but normal myelination in the posterior limb will assist differential diagnosis; alloisoleucine is a useful diagnostic marker and mutation analysis may be of prognostic value. These novel mutations Y256C and Y256X result in the clinical manifestation of a variant form of MSUD, expanding the mutation spectrum of this disease. Keywords Maple syrup urine disease Variant form BCKDHB gene Mutation