Features of clinical phenotype and genotype in children with Alport syndrome in a single-center study

Abstract:

Objective：To investigate the features of clinical phenotype and genotype in children with Alport syndrome（AS）. Methods：The clinical and laboratory data，renal biopsy results，and gene detection results of 28 children with AS who were treated in our de－partment from May 2013 to May 2017 were collected，and a retrospective analysis was performed to investigate the features of clinical phenotype and genotype. Results：Of all 28 children，21 had X-linked Alport syndrome（XLAS），1 had autosomal recessive Alport syndrome，4 had autosomal dominant Alport syndrome（ADAS），and 2 had XLAS and ADAS. All 28 children had hematuria as the initial manifestation；2 had hearing impairment，3 had ocular lesions，and 5 had renal dysfunction. Of all children，23 had a positive family history. Renal biopsy was performed for 17 children，among whom only 4 had typical pathological manifestations of AS under an electron microscope；immunofluorescence assay was performed for 16 children，among whom only 5 had absent expression of α3 and α5 chains. A total of 34 mutation sites were found，with 25 missense mutations，4 frameshift mutations，3 shear mutations，2 stop mutations，and 1 large fragment deletion，and 24 mutation sites had not been reported before. Conclusion：XLAS is the most common type of AS and missense mutation is the main type of pathogenic mutation. Hematuria is the most common clinical manifestation，with or without proteinuria，and extrarenal manifestations are rare. Renal biopsy shows minimal change disease in most children with AS，with atypical findings under an electron microscope，which leads to a high rate of missed diagnosis. Gene detection is an important method for the diagnosis of AS.