儿童溶血尿毒综合征及C3肾小球病的临床及基因分析

发布时间：2018-05-23 10:45

本文选题：C3肾小球病 + 溶血尿毒综合症　；参考：《南方医科大学》2017年硕士论文

【摘要】：第一部分儿童溶血尿毒综合征临床及病因分析目的:探讨我院儿童溶血尿毒综合征(Hemolytic uremic syndrome,HUS)的病因及其临床特点,以提高临床医生对该疾病的进一步认识,改善预后。方法:对我院2008年10月至2016年10月确诊为HUS患儿的临床资料进行回顾性分析。结果:10例HUS患儿中女4例,男6例,起病年龄0.1～8.7岁,平均(4.4±3.3)岁。8例有前驱感染史,其中6例有腹泻(其中1例为血便)。临床表现:10例患儿均伴有不同程度贫血、血小板降低、乳酸脱氢酶增高及肾脏受累;4例有水肿;5例伴有轻—中度高血压。3例有神经系统症状,其中1例有运动、语言发育迟缓,1例伴有肌张力低下、发育延迟,1例病程中出现抽搐。1例皮肤有瘀点;4例有黄疸。实验室检查:10例患儿均伴有低补体C3血症,5例患儿行H因子抗体、H因子检测,其中1例H因子抗体阳性,其余未见异常。3例有尿甲基丙二酸、血同型半胱氨酸升高,其中2例基因学检查分别有 MMACHC(p.27QR,p.203WX)、MMACHC(p.27QR)突变。3 例肾活检均符合溶血尿毒综合征肾损害,其中1例提示局灶增生性IgA肾病伴肾小管间质损害伴微血栓形成。治疗:7例给予血浆置换或新鲜冰冻血浆输注;6例伴有急性肾损伤,其中5例给予肾脏替代治疗;3例MMA患儿给予维生素B12、甜菜碱等治疗;部分患儿给予激素、免疫抑制剂治疗。10例患儿住院时间为4～60天,中位数33天,6例完全缓解,其中4例于0.5年内血、尿液检查及补体C3水平完全恢复正常,2例失访;2例部分缓解,其中1例血清补体C3于发病0.8年恢复正常,另外1例持续性低补体C3血症,感染后复发1次,最终均进入慢性肾脏病期;2例治疗无效办理出院。结论:HUS病因多样,早期可能均有旁路途径的激活参与疾病的进展;以腹泻起病但持续低补体C3血症的患儿应考虑应旁路途径相关基因异常或抗体的产生;不同病因治疗不同,MMA引起的HUS叶酸、甜菜碱可控制病情,持续补体旁路途径异常相关HUS需联合免疫制剂治疗。第二部分儿童C3肾小球病临床及基因分析目的:探讨我院儿童C3肾小球病(C3 glomerulopathy,C3G)的临床、病理、治疗方案及预后,提高临床医生对该类疾病的诊治水平,改善预后;另外,通过对儿童C3G的补体旁路途径相关基因的检测,了解C3G的遗传机制,进一步探索C3G基因与临床表型的关系。方法:对我院确诊为C3G患儿的临床资料进行回顾性分析,并对其预后转归进行随访;采用第一代基因测序技术对4例C3G患儿行旁路途径异常相关基因的检测。结果:7例C3G患儿中女4例,男3例,起病年龄1.5～10.4岁,平均(7.7±3.1)岁,至肾活检时间1～6月,平均(3.4±2.4)月,其中例5发病4.2年重复肾活检,确诊年龄1.8～13.3岁,平均(8.4±3.6)岁。临床特征:7例患儿中5例有大量蛋白尿、低蛋白血症,1例肉眼血尿,5例镜下血尿,6例低补体C3血症,2例伴有贫血,5例行H因子、H因子抗体检测,其中1例H因子降低,H因子抗体均阴性,诊断为肾炎型肾病综合征4例,单纯型肾病综合征1例,肾炎综合征2例。病理特征:免疫荧光显示1例仅有C3沉积,6例伴有其他免疫蛋白成分沉积。光镜表现为膜增生性肾小球肾炎(MPGN)3例,系膜增生性肾小球肾炎(MsPGN)1例,毛细血管内增生性肾小球肾炎(EnPGN)2例,毛细血管内增生性IgA肾病(EPIgAN)1例。电镜诊断致密物沉积病(DDD)3例,其余4例均符合光镜诊断,结合临床诊断为C3肾小球肾炎(C3GN)。治疗及随访:给予甲泼尼龙冲击后足量激素联合免疫抑制剂(环磷酰胺、吗替麦考酚酯、他克莫司)治疗,随访1.1～5.6年,平均(2.6±1.8)年,尿检完全正常4例,尿微量蛋白轻度增高伴少量镜下血尿2例,尿蛋白±～2+伴镜下血尿1例;血清补体C3恢复正常2例;肾功能均正常。4例患儿行基因测序,其中1例CFH基因有2个单核苷酸多肽SNP(p.H402Y、p.E936D),余未检测出异常。结论:C3G临床、病理表现多样,诊断需要肾脏病理结合临床、血清补体C3水平、补体相关调节蛋白及基因学检测;及早给予激素联合免疫抑制剂治疗可能会阻止部分C3G病程的进展,维持肾功能正常;1例患儿CFH基因有2个SNP(p.H402Y、β.E936D)。
[Abstract]:The first part of the clinical and etiological analysis of hemolytic uremic syndrome in children: To explore the etiology and clinical characteristics of Hemolytic uremic syndrome (HUS) in children in our hospital, so as to improve the further understanding of the disease by clinicians and improve the prognosis. Methods: the diagnosis of HUS in our hospital from October 2008 to October 2016 Results: there were 4 cases in 10 children with HUS, 6 males, 0.1 to 8.7 years old, and the average (4.4 + 3.3) years of.8 had a history of prodrome infection. 6 of them had diarrhea (including 1 for blood). Clinical manifestations: 10 cases were accompanied by different degrees of anemia, thrombocytopenia, increased lactate dehydrogenase and renal involvement; 4 edema; 5 cases of.3 with mild to moderate hypertension had nervous system symptoms, including 1 cases of exercise, language retardation, 1 cases with low muscular tension, delayed development, 1 cases of convulsions in 1 cases, and jaundice in 4 cases, 10 cases of children with hypocomplement C3, 5 children with H factor antibody, H factor detection, 1 of them. The H factor antibody was positive, and the others had no abnormal.3 cases with urinary methylmalonic acid and elevated blood homocysteine, of which 2 genetic tests were MMACHC (p.27QR, p.203WX), MMACHC (p.27QR) mutation of.3 cases were all conformed to hemolytic uremic syndrome renal damage, of which 1 cases showed focal proliferative IgA nephropathy with renal tubulointerstitial lesion accompanying micro Thrombus formation. Treatment: 7 cases were given plasma exchange or fresh frozen plasma infusion; 6 cases with acute renal injury, of which 5 cases were given renal replacement therapy; 3 cases of MMA children were given vitamin B12, betaine and other treatments; some children were given hormone, immunosuppressant treatment of.10 cases were 4~60 days, median 33 days, 6 cases complete remission, In 4 cases, blood, urine examination and complement C3 were completely recovered in 0.5 years, 2 cases were lost and 2 cases were partially remission, of which 1 cases of serum complement C3 returned to normal in 0.8 years, the other 1 cases of persistent low complement C3, 1 times after infection, and all of them all entered chronic renal disease, 2 cases were invalid and discharged. Conclusion: HUS causes various causes, In the early stage, there may be the activation of the bypass pathway in the disease. Children with diarrhea and persistent low complement C3 should consider the accessory pathway related gene abnormalities or the production of antibodies; different etiological treatments are different, MMA induced HUS folic acid, betaine can control the disease, and the persistent complement bypass pathway is associated with HUS associated immunization. Preparation therapy. Clinical and genetic analysis of C3 glomerulopathy in second children: To explore the clinical, pathological, treatment and prognosis of C3 C3 glomerulopathy (C3G) in children in our hospital, improve the diagnosis and treatment of this kind of disease by clinicians and improve the prognosis; and the detection of genes related to the complement pathway of C3G in children, To understand the genetic mechanism of C3G and to further explore the relationship between the C3G gene and clinical phenotype. Methods: the clinical data of children diagnosed with C3G in our hospital were analyzed retrospectively, and the prognosis of the patients was followed up, and the first generation gene sequencing technique was used to detect the ISO related genes in the bypass pathway of 4 children with C3G. Results: 7 cases of children with C3G were 4. 3 male cases, the onset age of 1.5 to 10.4 years old, average (7.7 + 3.1) years, to 1~6 months of renal biopsy, average (3.4 + 2.4) months, including 4.2 years of 4.2 years of renal biopsy in case 5, average age 1.8 to 13.3 years, average (8.4 +) years. Body C3, 2 cases of anemia, 5 cases of H factor and H factor antibody test, 1 cases of H factor decreased, H factor antibody was negative, 4 cases of nephritic nephrotic syndrome, 1 cases of nephrotic syndrome, 2 cases of nephritis syndrome. Pathological features: 1 cases of immunofluorescence showed only C3 deposition, 6 cases accompanied by other immunoglobulin deposits. Light microscopy table There were 3 cases of membranous proliferative glomerulonephritis (MPGN), 1 cases of mesangial proliferative glomerulonephritis (MsPGN), 2 cases of capillary proliferative glomerulonephritis (EnPGN), 1 cases of capillary proliferative IgA nephropathy (EPIgAN) in capillaries. 3 cases of DDD were diagnosed by electron microscopy. The remaining 4 cases were diagnosed as C3 glomerulonephritis (C3GN) combined with clinical diagnosis. Treatment and follow-up: a full dose of methylprednisolone combined with a sufficient hormone combined with immunosuppressive agents (cyclophosphamide, malcophenol ester, tacrolimus), followed up for 1.1 to 5.6 years, average (2.6 + 1.8) years, complete normal urine test 4 cases, urine microprotein slightly increased with a small number of microscopic hematuria in 2 cases, urinary protein + 2+ with microscopic hematuria 1 cases, serum complement C3 restorer 2 cases of normal normal.4 cases were sequenced. 1 cases of CFH gene had 2 single nucleotide polypeptides SNP (p.H402Y, p.E936D), and the abnormalities were not detected. Conclusion: C3G clinical and pathological manifestations are varied. The diagnosis needs renal pathological combined clinical, serum complement C3 level, complement related regulatory protein and genetic detection; and early excitation Treatment with combination of immunosuppressive drugs may prevent progression of some C3G and maintain normal renal function. In 1 children, CFH gene has 2 SNP (p.H402Y, beta.E936D).
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R726.9

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