本文選題：C3腎小球病 + 溶血尿毒綜合癥�。� 參考：《南方醫(yī)科大學》2017年碩士論文

【摘要】：第一部分 兒童溶血尿毒綜合征臨床及病因分析目的:探討我院兒童溶血尿毒綜合征(Hemolytic uremic syndrome,HUS)的病因及其臨床特點,以提高臨床醫(yī)生對該疾病的進一步認識,改善預后。方法:對我院2008年10月至2016年10月確診為HUS患兒的臨床資料進行回顧性分析。結(jié)果:10例HUS患兒中女4例,男6例,起病年齡0.1～8.7歲,平均(4.4±3.3)歲。8例有前驅(qū)感染史,其中6例有腹瀉(其中1例為血便)。臨床表現(xiàn):10例患兒均伴有不同程度貧血、血小板降低、乳酸脫氫酶增高及腎臟受累;4例有水腫;5例伴有輕—中度高血壓。3例有神經(jīng)系統(tǒng)癥狀,其中1例有運動、語言發(fā)育遲緩,1例伴有肌張力低下、發(fā)育延遲,1例病程中出現(xiàn)抽搐。1例皮膚有瘀點;4例有黃疸。實驗室檢查:10例患兒均伴有低補體C3血癥,5例患兒行H因子抗體、H因子檢測,其中1例H因子抗體陽性,其余未見異常。3例有尿甲基丙二酸、血同型半胱氨酸升高,其中2例基因?qū)W檢查分別有 MMACHC(p.27QR,p.203WX)、MMACHC(p.27QR)突變。3 例腎活檢均符合溶血尿毒綜合征腎損害,其中1例提示局灶增生性IgA腎病伴腎小管間質(zhì)損害伴微血栓形成。治療:7例給予血漿置換或新鮮冰凍血漿輸注;6例伴有急性腎損傷,其中5例給予腎臟替代治療;3例MMA患兒給予維生素B12、甜菜堿等治療;部分患兒給予激素、免疫抑制劑治療。10例患兒住院時間為4～60天,中位數(shù)33天,6例完全緩解,其中4例于0.5年內(nèi)血、尿液檢查及補體C3水平完全恢復正常,2例失訪;2例部分緩解,其中1例血清補體C3于發(fā)病0.8年恢復正常,另外1例持續(xù)性低補體C3血癥,感染后復發(fā)1次,最終均進入慢性腎臟病期;2例治療無效辦理出院。結(jié)論:HUS病因多樣,早期可能均有旁路途徑的激活參與疾病的進展;以腹瀉起病但持續(xù)低補體C3血癥的患兒應考慮應旁路途徑相關(guān)基因異�；蚩贵w的產(chǎn)生;不同病因治療不同,MMA引起的HUS葉酸、甜菜堿可控制病情,持續(xù)補體旁路途徑異常相關(guān)HUS需聯(lián)合免疫制劑治療。第二部分 兒童C3腎小球病臨床及基因分析目的:探討我院兒童C3腎小球病(C3 glomerulopathy,C3G)的臨床、病理、治療方案及預后,提高臨床醫(yī)生對該類疾病的診治水平,改善預后;另外,通過對兒童C3G的補體旁路途徑相關(guān)基因的檢測,了解C3G的遺傳機制,進一步探索C3G基因與臨床表型的關(guān)系。方法:對我院確診為C3G患兒的臨床資料進行回顧性分析,并對其預后轉(zhuǎn)歸進行隨訪;采用第一代基因測序技術(shù)對4例C3G患兒行旁路途徑異常相關(guān)基因的檢測。結(jié)果:7例C3G患兒中女4例,男3例,起病年齡1.5～10.4歲,平均(7.7±3.1)歲,至腎活檢時間1～6月,平均(3.4±2.4)月,其中例5發(fā)病4.2年重復腎活檢,確診年齡1.8～13.3歲,平均(8.4±3.6)歲。臨床特征:7例患兒中5例有大量蛋白尿、低蛋白血癥,1例肉眼血尿,5例鏡下血尿,6例低補體C3血癥,2例伴有貧血,5例行H因子、H因子抗體檢測,其中1例H因子降低,H因子抗體均陰性,診斷為腎炎型腎病綜合征4例,單純型腎病綜合征1例,腎炎綜合征2例。病理特征:免疫熒光顯示1例僅有C3沉積,6例伴有其他免疫蛋白成分沉積。光鏡表現(xiàn)為膜增生性腎小球腎炎(MPGN)3例,系膜增生性腎小球腎炎(MsPGN)1例,毛細血管內(nèi)增生性腎小球腎炎(EnPGN)2例,毛細血管內(nèi)增生性IgA腎病(EPIgAN)1例。電鏡診斷致密物沉積病(DDD)3例,其余4例均符合光鏡診斷,結(jié)合臨床診斷為C3腎小球腎炎(C3GN)。治療及隨訪:給予甲潑尼龍沖擊后足量激素聯(lián)合免疫抑制劑(環(huán)磷酰胺、嗎替麥考酚酯、他克莫司)治療,隨訪1.1～5.6年,平均(2.6±1.8)年,尿檢完全正常4例,尿微量蛋白輕度增高伴少量鏡下血尿2例,尿蛋白±～2+伴鏡下血尿1例;血清補體C3恢復正常2例;腎功能均正常。4例患兒行基因測序,其中1例CFH基因有2個單核苷酸多肽SNP(p.H402Y、p.E936D),余未檢測出異常。結(jié)論:C3G臨床、病理表現(xiàn)多樣,診斷需要腎臟病理結(jié)合臨床、血清補體C3水平、補體相關(guān)調(diào)節(jié)蛋白及基因?qū)W檢測;及早給予激素聯(lián)合免疫抑制劑治療可能會阻止部分C3G病程的進展,維持腎功能正常;1例患兒CFH基因有2個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).
【學位授予單位】：南方醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R726.9

【參考文獻】

相關(guān)期刊論文 前3條

1 李春珍;張東風;劉玲;李坤芬;葛蘭蘭;王靜霞;;兒童繼發(fā)于甲基丙二酸血癥的微血管性溶血及腎臟損傷病例分析[J];臨床兒科雜志;2016年03期

2 張宏博;黃建萍;;毛細血管內(nèi)增生性腎炎轉(zhuǎn)變?yōu)槟ぴ錾阅I炎1例報告[J];臨床兒科雜志;2015年03期

3 張濤;章海濤;徐峰;黃倩;王金泉;曾彩虹;陳慧梅;劉志紅;;C3腎病的臨床病理特征及預后分析[J];腎臟病與透析腎移植雜志;2014年05期

，

本文編號：1924407