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学科主题: 临床医学
题名:
Clinical, biochemical, and molecular analysis of combined methylmalonic acidemia and hyperhomocysteinemia (cblC type) in China
作者: 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
发表日期: 2010-12-01
DOI: 10.1007/s10545-010-9217-0
卷: 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
所属项目编号: 2006AB105A05 ; 2006BA105A07 ; 2007AA02Z447 ; 2008ZD001 ; 2006043
项目资助者: 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
WOS记录号: WOS:000209022100071
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50248
Appears in Collections:北京大学第一临床医学院_儿科_期刊论文

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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

Recommended Citation:
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.
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