Abstract: Objective    To analyze the genotype and phenotype characteristics of 42 pediatric patients with Alport syndrome （AS） and explore the efficacy of angiotensin-converting enzyme inhibitor （ACEI） and angiotensin receptor blocker （ARB） in different gene mutation types of AS. Methods    A total of 42 patients diagnosed with AS admitted to the Pediatrics Department of Guangzhou Red Cross Hospital and the Pediatrics Department of Guangzhou First People's Hospital from January 2016 to December 2022 were selected. All confirmed cases underwent genetic testing for diagnosis and received ACEI and/or ARB treatment. The follow-up period was 3 years（from January 2020 to December 2022），during which the age，gender，course of the disease and genetic testing results were recorded，and monitoring of laboratory indicators during the follow-up period were compared. The laboratory indicators included 24-hour urine protein quantification （mg），urine red blood cell count，plasma albumin （ALB，g/L），blood urea nitrogen （BUN，mmol/L），serum creatinine （Scr，μmol/L），total cholesterol （TC，mmol/L），and prognosis. Results    Among the 42 patients with AS，there were 16 cases of COL4A3/COL4A4 gene mutation and 26 cases of COL4A5 gene mutation. There were 19 cases of missense mutation and 23 cases of non-missense mutation，including 11 cases of nonsense mutation，9 cases of splicing mutation and 3 cases of frameshift mutation. Among them，16 patients had a positive family history of AS，and missense mutation and non-missense mutation had statistical signifi-cance in positive family history （P < 0.05）. AS usually started with gross hematuria or microscopic hematuria，and gradually developed proteinuria. There was no statistical statistical difference in manifestations of onset significance between missense mutation and non-missense mutation （P > 0.05）. However，patients with non-missense mutations had large amounts of hematuria and nephrotic level proteinuria （P < 0.05），were prone to extrarenal manifestations such as hearing and eye abnormalities，and entered end-stage renal disease earlier. Early application of ACEI and ARB can effectively reduce hematuria and proteinuria （P < 0.05） and delay the progression of renal failure. Compared with missense mutations，hematuria and proteinuria decreased more significantly after treatment in patients with non-missense mutations，but remained at a higher level. Conclusion    Genotype affects the severity of disease in AS patients. ACEI and ARB drugs can significantly reduce hematuria and proteinuria in AS patients，delaying the progression to ESRD，and its efficacy may be related to genotype.

Key words: Alport syndrome, genotype-phenotype, clinical treatment, follow-up

摘要： 目的    分析42例儿童Alport综合征（Alport syndrome，AS）的基因型与表型特点，探讨血管紧张素转化酶抑制剂（angiotensin-converting enzyme inhibitor，ACEI）和血管紧张素Ⅱ受体阻滞剂（angiotensin receptor blocker，ARB）在Alport综合征不同基因突变类型的疗效。方法    选取2016年1月至2022年12月期间在广州市红十字会医院儿科及广州市第一人民医院儿科收治的Alport综合征的患儿共42例，所有确诊病例均行基因检测确诊，同时接受ACEI和（或）ARB治疗。随访3年（2020年1月至2022年12月），记录患儿年龄、性别、病程、基因检测分型结果，比较监测随访期间的检验指标，包括：24h尿蛋白定量（mg）、尿红细胞计数（个/μL）、血浆清蛋白（ALB，g/L）、尿素氮（BUN，mmol/L）、血肌酐（Scr，μmol/L）、总胆固醇（TC，mmol/L）情况以及预后。结果    42例AS患儿中，COL4A3/COL4A4基因突变16例，COL4A5基因突变26例。基因检测提示错义突变有19例，非错义突变有23例，包括无义突变有11例，剪接突变9例，移码突变3例。其中16例AS患儿有阳性家族史，错义突变和非错义突变在阳性家族史中差异有统计学意义（P<0.05）。AS常以肉眼血尿或镜下血尿起病，并逐渐出现蛋白尿，错义突变与非错义突变起病时表现形式差异无统计学意义（P>0.05）；但非错义突变患儿有大量血尿及肾病水平的蛋白尿（P<0.05），容易出现听力异常和眼部异常等肾外表现，并更早进入终末期肾病（end stage renal disease，ESRD）。早期应用ACEI联合ARB药物能有效降低血尿及蛋白尿（P<0.05），延缓肾功能衰竭的进展。与错义突变相比，非错义突变患儿治疗后血尿和蛋白尿下降幅度更大，但仍维持在较高水平。结论    基因型影响AS患儿疾病严重程度，ACEI联合ARB药物可显著降低AS患儿血尿及蛋白尿，延缓进展至ESRD，其疗效可能与基因型相关。

关键词: Alport综合征, 基因型-表型, 临床治疗, 随访