甲基丙二酸血症伴同型半胱氨酸血症患儿临床及基因突变分析  

Clinical and gene mutation analysis in patients with methylmalonic acidemia and homocysteinemia

作　　者：韩连书[1] 王斐[1] 胡宇慧[1] 叶军[1] 邱文娟[1] 张雅芬[1] 高晓岚[1] 王瑜[1] 金晶[1] 顾学范[1] 

机构地区：[1]上海交通大学医学院附属新华医院,上海市儿科医学研究所,内分泌、遗传代谢病研究室,上海200092

出　　处：《中华内分泌代谢杂志》2009年第4期405-408,共4页Chinese Journal of Endocrinology and Metabolism

基　　金：十一五国家科技支撑计划课题（2006AB105A05,2006BA105A07）;国家高技术发展计划（2007AA02Z447）;上海市卫生局科研课题（2006043）

摘　　要：目的对甲基丙二酸血症合并同型半胱氨酸血症患儿进行临床诊治分析及基因突变检测。方法诊断主要依靠串联质谱检测血中的丙酰肉碱水平、气相色谱-质谱检测尿中甲基丙二酸水平及荧光偏振免疫法检测血同型半胱氨酸水平；治疗给予维生素B12、甜菜碱、左旋肉碱、叶酸及维生素B6；基因突变分析应用PCR扩增MMACHC基因外显子，直接测序。结果14例患儿中12例经治疗后，临床症状明显好转，血中丙酰肉碱、同型半胱氨酸及尿中甲基丙二酸显著降低，2例患儿放弃治疗死亡。12例患儿检测到5种MMACHC基因突变，2例未检测到突变。7例为609G〉A纯合突变，5例为609G〉A伴658_660delAAG（2例）、567_568insT、394C〉T和217C〉T杂合突变，其中658_660delAAG和567_568insT为尚未报道的突变。结论甲基丙二酸血症合并同型半胱氨酸血症患儿经合理治疗可达到较好的临床效果。基因突变检测表明609G〉A为中国患儿的热点突变。Objective Methylmalonic acidemia combined with homocysteinemia is an inborn error of cohalamin metabolism with an autosomal recessive mode. The cbl C type is the most common form of this disease, in which the gene was named MMACHC. This study was aimed to analyse the diagnosis, treatment and gene mutations in 14 patients. Methods Measurements of C3 （propionylcarnitine） , C3/C0 （ free earnitine） and C3/C2 （aeetylcarnitine） in blood were detected by tandem massspectrometry; urine methylmalonic acid were determined by gas-chromatography mass spectrometry; and serum homosysteine were determined with the method of fluorescence polarization immunization. These patients were treated with vitamin B12, L-carnitine, betaine, folic acid and vitamin B6. The MMACHC gene was screened by PCR combined with DNA direct sequencing in 14 Chinese patients. Results With treatment clinical symptoms of 12 patients were improved obviously; the levels of blood propionylearnitine and homocysteine as well as urine methylmalonic acid were decreased. Two patients were dead without treatments. In this study, five different mutations in 12 patients were detected, only one polymorphism was found in one patient, and in another patient no mutation was detected. We found 609G〉A homozygotic mutations in 7 patients, and heterozygotie ones of 609G〉A with 658_660delAAG,567_568insT, 394C〉T and 217C〉T in 5 patients, in which 658_660delAAG and 567_568insT were novel mutations. Conclusion The patients with methylmalonic acidemia and homocysteinemia could have an improved outcome after reasonable treatments. The gene mutation detection suggests that 609G〉A （W203X） may be the hot spot mutation of MMACHC gene in Chinese patients.

关 键 词：甲基丙二酸血症 同型半胱氨酸血症 诊断 治疗 基因突变 

分 类 号：R686[医药卫生—骨科学]