关键词: Alport综合征, 基因型-表型, 临床治疗, 随访

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