Two novel mutations in the BCKDHB gene that cause maple syrup urine disease
Background: Maple syrup urine disease (MSUD) is a rare metabolic disorder of autosomal recessive inheritance caused by decreased activity of branched-chain α-ketoacid dehydrogenase complex (BCKD). Mutations in the three genes (BCKDHA, BCKDHB and DBT) are associated with MSUD. Here, we describe the p...
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Elsevier
2018-10-01
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| Series: | Pediatrics and Neonatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1875957216301541 |
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| author | Bingjuan Han Bingchao Han Bin Guo Yingxia Liu Zhiyang Cao |
| author_facet | Bingjuan Han Bingchao Han Bin Guo Yingxia Liu Zhiyang Cao |
| author_sort | Bingjuan Han |
| collection | DOAJ |
| description | Background: Maple syrup urine disease (MSUD) is a rare metabolic disorder of autosomal recessive inheritance caused by decreased activity of branched-chain α-ketoacid dehydrogenase complex (BCKD). Mutations in the three genes (BCKDHA, BCKDHB and DBT) are associated with MSUD. Here, we describe the presenting symptoms, clinical course and gene mutation analysis of a Chinese boy with MSUD. Methods: Plasma amino acid analysis was performed by tandem mass spectrometry and the levels of organic acids in urine were measured with gas chromatography-mass spectrometry. The BCKDHB gene was sequenced by Sanger method. Furthermore, the significance of the novel mutations was predicted by Polyphen and Mutationtaster. After diagnosis, the patient was fed with protein-restricted diet to reduce intake of BCAA and was treated with l-carnitine. Metabolic parameters, clinical presentation and mental development were followed up. Results: The patient was diagnosed as MSUD. Two novel BCKDHB mutations (c.523 T > C and c.478-25_552del100) were identified. In silico analysis predicted that the two mutations were “disease causing”. The boy tolerated the treatment well and had symptomatic improvement. He presented with mild hypotonia and had nearly normal DQ scores at the age of 10 months. The two novel mutations resulted in the clinical manifestations of MSUD. Our results may reflect the heterogeneity of the pathogenic variants found in patients with MSUD. Key Words: BCAA, BCKD, BCKDHB, gene mutation, maple syrup urine disease |
| format | Article |
| id | doaj-art-bee9b2ab33f84c4599a60f120f03f421 |
| institution | OA Journals |
| issn | 1875-9572 |
| language | English |
| publishDate | 2018-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pediatrics and Neonatology |
| spelling | doaj-art-bee9b2ab33f84c4599a60f120f03f4212025-08-20T02:18:58ZengElsevierPediatrics and Neonatology1875-95722018-10-0159551551910.1016/j.pedneo.2018.01.006Two novel mutations in the BCKDHB gene that cause maple syrup urine diseaseBingjuan Han0Bingchao Han1Bin Guo2Yingxia Liu3Zhiyang Cao4Jinan Maternal and Child Care Hospital, Jinan, 250001, Shandong Province, ChinaJinan Maternal and Child Care Hospital, Jinan, 250001, Shandong Province, ChinaJinan Maternal and Child Care Hospital, Jinan, 250001, Shandong Province, ChinaJinan Maternal and Child Care Hospital, Jinan, 250001, Shandong Province, China; Department of Immunology, Nanjing Medical University, Nanjing, 21166, Jiangsu Province, China; Corresponding author. 101Longmian Avenue, Jiangning District, Nanjing, Jiangsu Province, China. Fax: +86 25 86868499.Nanjing Jiangning Hospital, Affiliated to Nanjing Medical University, Nanjing 211100, Jiangsu Province, China; Corresponding author. No. 168, Gushan Road, Jiangning District, Nanjing, Jiangsu Province, China. Fax: +86 25 52281256.Background: Maple syrup urine disease (MSUD) is a rare metabolic disorder of autosomal recessive inheritance caused by decreased activity of branched-chain α-ketoacid dehydrogenase complex (BCKD). Mutations in the three genes (BCKDHA, BCKDHB and DBT) are associated with MSUD. Here, we describe the presenting symptoms, clinical course and gene mutation analysis of a Chinese boy with MSUD. Methods: Plasma amino acid analysis was performed by tandem mass spectrometry and the levels of organic acids in urine were measured with gas chromatography-mass spectrometry. The BCKDHB gene was sequenced by Sanger method. Furthermore, the significance of the novel mutations was predicted by Polyphen and Mutationtaster. After diagnosis, the patient was fed with protein-restricted diet to reduce intake of BCAA and was treated with l-carnitine. Metabolic parameters, clinical presentation and mental development were followed up. Results: The patient was diagnosed as MSUD. Two novel BCKDHB mutations (c.523 T > C and c.478-25_552del100) were identified. In silico analysis predicted that the two mutations were “disease causing”. The boy tolerated the treatment well and had symptomatic improvement. He presented with mild hypotonia and had nearly normal DQ scores at the age of 10 months. The two novel mutations resulted in the clinical manifestations of MSUD. Our results may reflect the heterogeneity of the pathogenic variants found in patients with MSUD. Key Words: BCAA, BCKD, BCKDHB, gene mutation, maple syrup urine diseasehttp://www.sciencedirect.com/science/article/pii/S1875957216301541 |
| spellingShingle | Bingjuan Han Bingchao Han Bin Guo Yingxia Liu Zhiyang Cao Two novel mutations in the BCKDHB gene that cause maple syrup urine disease Pediatrics and Neonatology |
| title | Two novel mutations in the BCKDHB gene that cause maple syrup urine disease |
| title_full | Two novel mutations in the BCKDHB gene that cause maple syrup urine disease |
| title_fullStr | Two novel mutations in the BCKDHB gene that cause maple syrup urine disease |
| title_full_unstemmed | Two novel mutations in the BCKDHB gene that cause maple syrup urine disease |
| title_short | Two novel mutations in the BCKDHB gene that cause maple syrup urine disease |
| title_sort | two novel mutations in the bckdhb gene that cause maple syrup urine disease |
| url | http://www.sciencedirect.com/science/article/pii/S1875957216301541 |
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