非典型溶血尿毒综合征患儿14例临床表型与基因型分析

发布时间：2018-02-14 23:00

本文关键词： 非典型溶血尿毒综合征儿童临床表型基因　出处：《中国循证儿科杂志》2017年01期 　论文类型：期刊论文

【摘要】：目的对非典型溶血尿毒综合征(aHUS)临床表型和基因型分析了解与预后的关系。方法纳入临床表现符合血栓性微血管病(TMA)的患儿,通过ELISA法行ADAMTS13酶活性的检测,对ADAMTS13酶活性10%,且排除其他类型HUS,行肾脏267个基因panel(包括aHUS已知的与发病相关的C3、C4、C5、CFH、CFB、CFI、MCP、CFHR1、CFHR3、CFHR5、THBD、PLG、DGKE)二代测序,对测序结果阳性的基因行sanger验证。提取纳入的aHUS患儿的随访资料,比较基因突变与未突变患儿预后,系统检索文献,行aHUS临床表型与基因文献复习。结果 14例aHUS患儿进入本文分析,男6例,女8例,5例累及肾脏以外系统。基因检测阳性和阴性者SCr分别为335.3和247.8,eGFR分别为28.8和21.2,C3降低分别为3例和4例,随访时间1~67个月,末次随访结局:基因检测阳性和阴性死亡分别为2例和0例,复发分别为2例和0例,终末期肾病(ESRD)分别为3例和0例,eGFR分别为48和103.7。检索Pubmed数据库,对包括本文病例在内的成人(148例)和儿童(154例)aHUS病例行临床特征和基因型分析,男性病例儿童多于成人,差异有统计学意义;前驱感染(消化和呼吸道)儿童较成人比例高,差异有统计学意义;除神经系统受累、肺泡内出血及高血压外,儿童较成人更易累及其他系统(肝炎、胰腺炎等多器官受损);成人Scr异常高值大于儿童,差异有统计学意义。CFH突变率欧洲人群高于亚洲,差异有统计学意义。结论儿童和成人CFH突变均较未突变的aHUS病例预后差,儿童较成人aHUS病例更易累及肾脏、神经以外的系统。
[Abstract]:The purpose of atypical hemolytic uremic syndrome (aHUS) clinical phenotype and genotype analysis to understand the relationship between the prognosis. Methods included clinical manifestations with thrombotic microangiopathy (TMA) were detected by ADAMTS13 ELISA method for enzyme activity, enzyme activity of ADAMTS13 was 10%, and the removal of other types of HUS, kidney 267 the panel gene (including the known aHUS correlated with the incidence of C3, C4, C5, CFH, CFB, CFI, MCP, CFHR1, CFHR3, CFHR5, THBD, PLG, DGKE) two generation sequencing, the sequence of the gene for Sanger positive verification. Extraction incorporating aHUS children with follow-up data, gene mutation and no mutation of prognosis, literature retrieval system, aHUS clinical phenotype and literature review. The results of this gene into aHUS with analysis of 14 cases, male 6 cases, female 8 cases, 5 cases of renal involvement outside the system. Gene detection of positive and negative SCr respectively 335.3 and 247.8, 28.8 and 21.2 eGFR respectively. C3, decreased respectively 3 cases and 4 cases, the follow-up time was 1~67 months. At the end of the follow-up outcome: genetic testing positive and negative death were 2 cases and 0 cases of recurrence were 2 cases and 0 cases of end-stage renal disease (ESRD) were 3 cases and 0 cases, respectively 48 and eGFR 103.7. Pubmed of data retrieval of library, including this case, adult (148 cases) and children (154 cases) underwent aHUS analysis of clinical characteristics and genotypes of male children than in adults, the difference was statistically significant; infection (digestive and respiratory) a high proportion of children than in adults, the difference was statistically significant; except nerve system involvement, intra alveolar hemorrhage and hypertension in children than in adults, more easily involved in other systems (hepatitis, pancreatitis and multiple organ damage); abnormal high Scr value is greater than the adult children, there was a significant difference between the mutation rate of.CFH is higher than that of European populations in Asia, the difference was statistically significant. Conclusion children and The prognosis of adult CFH mutations is worse than that of non mutant aHUS cases, and children with adult aHUS are more likely to be involved in the kidney and outside nervous system.

【作者单位】：复旦大学附属儿科医院肾脏科上海市肾脏发育和儿童肾脏病研究中心;复旦大学附属儿科医院风湿科;复旦大学附属儿科医院转化医学中心;
【分类号】：R726.9

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