CFHR1、CFHR3基因异常相关的非典型溶血尿毒综合征患儿的临床特征

Clinical features of atypical hemolytic uremic syndrome with CFHR1, CFHR3 genetic abnormalities in children

目的分析CFHR1、CFHR3基因异常的非典型溶血尿毒综合征（aHUS）患儿的临床特征。方法收集13例aHUS患儿的临床、病理资料及CFHR1、CFHR3基因检测结果，回顾性分析其临床特点、病理特点及治疗和预后，结合相关基因的检测结果进行临床特征分析。结果13例aHUS患儿纳入研究。其中男9例，女4例；年龄1.5～13.0岁。13例患儿除具有特征性的HUS三联征外，均有恶心、呕吐、腹痛或腹胀等胃肠道症状，但均无腹泻；均表现为大量蛋白尿，补体C3均下降；12例合并高血压。3例患儿进行了肾脏穿刺活检。患儿在确诊后均采用了血浆置换治疗，治疗后1例患儿为慢性肾脏病3期，余肾功能均恢复正常，蛋白尿消失或明显减轻，补体C3均恢复正常。在13例患儿中，CFH基因均未发现突变，6例有CFHR1/CFHR3基因缺失，1例CFHR1基因纯合缺失，2例CFHR1基因纯合突变，1例CFHR1基因杂合突变，2例CFHR1杂合缺失，1例CFHR1、CFHR3基因拷贝数增加。结论CFHR1、CFHR3基因异常的aHUS患儿肾功能损害重，补体下降突出，应以强化血浆置换为主要治疗方式，需要尽早进行，且血浆置换次数多，血浆用量大，且相对易复发。

Objective To analyze the clinical features of atypical hemolytic uremic syndrome（aHUS） with CFHR1, CFHR3 genetic abnormalities in children.Methods The clinical, pathological data and CFHR1, CFHR3 genetic test Results of 13 patients with aHUS were collected.A retrospective analysis of the clinical characteristics, pathological features, treatment and prognosis, and an analysis of the clinical manifestations according to the result of genetic testing were conducted.Results Thirteen aHUS patients were included in the study, including 9 male and 4 female, ranging in age from 1 year and a half to 13 years.All the patients had the typical clinical manifestations, and all patients had gastrointestinal symptoms such as nausea, vomiting, abdominal pain or bloating, and so on, but no diarrhea.All the patients showed massive proteinuria, complement C3 decrease; 12 cases with hypertension.Three patients underwent renal biopsy.All the patients were treated by plasmapheresis.After treatment, 1 patient was chronic kidney disease, others had normal renal function, and proteinuria either disappeared or was significantly reduced, but complement C3 was normal.CFH gene of the 13 patients was normal.CFHR1/CFHR3 gene had deletion in 6 cases; CFHR1 gene had homozygous deletion in 1 case; CFHR1 gene homozygous mutation in 2 cases; CFHR1 gene heterozygous mutation in 1 case; CFHR1 gene loss of heterozygosity in 2 cases; CFHR1 and CFHR3 increased gene copy number in 1 case.Conclusions aHUS with CFHR1, CFHR3 genetic abnormalities in children had severe renal injury, and decrease of complement was prominent.Plasmapheresis therapy was recommended as key treatment, which should be earlier and intensive.And this kind of aHUS is easy to relapse.