迟发型甲基丙二酸血症二家系的临床及基因突变分析  

Analysis of clinical features and gene mutations in two Chinese pedigrees with late-onset methylmalonic acidemia,cblC type

作　　者：崔冬[1] 陈淑丽[2] 温鹏强[1] 胡宇慧[2] 陈小文[1] 沈丹[3] 袁泉[2] 宋萍[2] 廖建湘[2] 李成荣[1] 

机构地区：[1]深圳市儿童医院儿科研究所,518026 [2]深圳市儿童医院遗传代谢专科,518026 [3]深圳市儿童医院检验科,518026

出　　处：《中华儿科杂志》2010年第6期469-472,共4页Chinese Journal of Pediatrics

摘　　要：目的 对2个迟发型甲基丙二酸血症家系临床特点及MMACHC基因突变情况进行研究.方法 对2例患儿的临床特点、诊疗情况进行分析.应用聚合酶链反应与DNA直接测序法对2个家系共6名成员进行MMACHC基因突变检测.结果 2例患儿发病年龄分别为13岁和12岁,均以神经系统异常就诊,表现为运动、语言、智力发育落后及倒退.例1伴有贫血,例2表现为类似病毒性脑炎的症状,出现脑萎缩.尿有机酸分析示甲基丙二酸大量升高,检测血清同型半胱氨酸浓度也增高明显.经维生素B12治疗后症状迅速改善.随访至今,2例明显好转.例1被检出两个突变c.482G〉A和c.658_660delAAG,前者来源于患儿母亲,后者来自父亲;例2被检出c.482G〉A及c.609G〉A,患儿父母分别携带这两个突变.所有突变均发生在第4外显子上,均为杂合子.c.482G〉A为错义突变,导致精氨酸→谷氨酰胺（R161Q）;c.609G〉A为无义突变,由色氨酸→终止密码（W203X）;c.658_660delAAG为缺失突变,造成一个赖氨酸的缺失.结论 迟发型甲基丙二酸血症临床表现多样性,两例患儿均以神经系统异常发病,1例伴有血液系统的改变.2例患儿均为维生素B12治疗有效型.基因突变均发生在第4外显子上,c.482G〉A可能与迟发型有一定的相关性.objective CblC is tlle most common type of methylmalonic acidemia with homocysteinemia.MMACHC is the coding gene.This study aimed at understanding clinical features and gene mutations in 2 Chinese pedigrees who had late-onset methylmalonic acidemia complicted with homocys-teinemia.Method The clinical data of 2 cases were analyzed.The MMACHC gene mutation was detected using polymerase chain reaction（PCR）and DNA sequencing.Result The age of onset was 13 years and 12 years.respectively.They both presented with nervous system symptoms.The main clinical features were developmental retardation and regradation,including motion,speech and intelligence.One patient complained of anemia.The other patient was misdiagnosed as having a viral encephalitis.Both patients showed remarkable elevation of methylmalonic aicd and homocysteine levels in urine.Both had received therapy with vitamin B12. The symptoms were rapidly relieved.The follow-up till now showed apparent improvement in the 2 cases.Three mutations in the MMACHC gene were found in the two Chinese pedigrees.Both patients were compound heterozygotes of two mutant alleles：one patient had a G-to-A transition at nucleotide 482（G482A）that caused an arginine-to-glutamine substitution at position 161 of the protein（R161Q）,and a deletion of AAG at nucleotide 658_660（658_660delAAG）which resulted in lysine deleting at position 220 of the protein（K220del）;the other patient had a G482A and a G-to-A transition at nucleotide 609（G609A）that caused a tryptophan-to-termination codon substitution at position 203 of the protein（W203X）.Otherwise,the authors also detected parents of two families.Each had a heterozygote of one mutation.Conclusion Late-onset methymalonic acidemia patients had a variety of clinical manifestation,the first symptom WaS mainly abnormality of nervous system.One case was accompanied with hematological abnormalities.Two patients were vitamin B12 responsive.In this study,the mutations were all detected on the fourth exon,the G482A mutat

关 键 词：甲基丙二酸 维生素B12 基因 突变 

分 类 号：R725.8[医药卫生—儿科]