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学科主题临床医学
Clinical, biochemical, and molecular analysis of combined methylmalonic acidemia and hyperhomocysteinemia (cblC type) in China
Wang, Fei1; Han, Lianshu1; Yang, Yanling2; Gu, Xuefan1; Ye, Jun1; Qiu, Wenjuan1; Zhang, Huiwen1; Zhang, Yafen1; Gao, XiaoLan1; Wang, Yu1
刊名JOURNAL OF INHERITED METABOLIC DISEASE
2010-12-01
DOI10.1007/s10545-010-9217-0
suppl.3页:S435-S442
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism ; Genetics & Heredity
研究领域[WOS]Endocrinology & Metabolism ; Genetics & Heredity
英文摘要

The most common inborn error of cobalamin (cbl) metabolism in China is the cblC type characterized by combined methylmalonic acidemia and hyperhomocysteinemia. The clinical presentation is relatively nonspecific, such as feeding difficulty, recurrent vomiting, hypotonia, lethargy, seizures, progressive developmental delay, and mental retardation, together with anemia and metabolic acidosis. More specific biochemical findings include high levels of propionylcarnitine (C3), free carnitine (C3/C0), and acetylcarnitine (C3/C2) measured by tandem mass spectrometry (MS/MS), elevation of methylmalonic acid (MMA) measured by gas chromatography-mass spectrometry (GC-MS), and increased total homocysteine with normal or decreased methionine. We report on 50 Chinese patients with combined methylmalonic acidemia and hyperhomocysteinemia. Forty-six belonged to the cblC complementation group. Mutation analysis of the MMACHC gene was performed to characterize the mutational spectrum of cblC deficiency, and 17 different mutations were found. Most were clustered in exons 3 and 4, accounting for 91.3% of all mutant alleles. Two mutations were novel, namely, c.315 C>G (p.Y105X) and c.470 G>C(p.W157S). In terms of genotype-phenotype correlation, the c.609 G>A mutation was associated with early-onset disease when homozygous. Unlike previous reports from other populations, c.609 G>A (p.W203X) was the most frequent cblC mutation detected in our study of Chinese patients, affecting 51 of 92 MMACHC alleles (55.4%). The high prevalence of this nonsense mutation could have potential therapeutic significance for Chinese cblC patients. Besides traditional approaches consisting of hydroxocobalamin injections, carnitine, betaine, and protein restriction, novel drugs that target premature termination codons may have a role in the future.

语种英语
WOS记录号WOS:000209022100071
项目编号2006AB105A05 ; 2006BA105A07 ; 2007AA02Z447 ; 2008ZD001 ; 2006043
资助机构Technology Pillar Program in the Eleventh Five-year Plan Period ; National High Technology Research and Development Program ; Key Subject of Shanghai Municipality ; Scientific Research Foundation Project of Shanghai Municipality
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50248
专题北京大学第一临床医学院_儿科
作者单位1.Shanghai Jiao Tong Univ, Sch Med, Dept Pediat Endocrinol & Genet Metab, Shanghai Inst Pediat Res,Xinhua Hosp, Shanghai 200092, Peoples R China
2.Beijing Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China
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GB/T 7714
Wang, Fei,Han, Lianshu,Yang, Yanling,et al. Clinical, biochemical, and molecular analysis of combined methylmalonic acidemia and hyperhomocysteinemia (cblC type) in China[J]. JOURNAL OF INHERITED METABOLIC DISEASE,2010,suppl.3:S435-S442.
APA Wang, Fei.,Han, Lianshu.,Yang, Yanling.,Gu, Xuefan.,Ye, Jun.,...&Wang, Yu.(2010).Clinical, biochemical, and molecular analysis of combined methylmalonic acidemia and hyperhomocysteinemia (cblC type) in China.JOURNAL OF INHERITED METABOLIC DISEASE,suppl.3,S435-S442.
MLA Wang, Fei,et al."Clinical, biochemical, and molecular analysis of combined methylmalonic acidemia and hyperhomocysteinemia (cblC type) in China".JOURNAL OF INHERITED METABOLIC DISEASE suppl.3(2010):S435-S442.
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