Genetic, Clinical, and Pathologic Backgrounds of Children With X-Linked Alport Syndrome in China: A Monocenter Study

Abstract

Background. Characteristics of X-linked Alport syndrome (XLAS) in a cohort of Chinese children. Methods. This work is a retrospective study covering the clinical information, pathological data, and gene sequencing results of 32 cases with XLAS from 2011 to 2022. Results. Among these 32 patients, the youngest age of onset was 3 months. Renal biopsy was performed on 29 children. The lamellated glomerular basement membrane was observed in 19 children using electron microscopy (65.5%). Of the 26 samples tested, 73.1% were found to be negative for collagen-a5 under immunohistochemical staining, showing clinical significance. Next-generation sequencing (NGS) detected 27 pathogenic gene mutations. A total of 15.4% of patients carried de novo mutations. Conclusions. The boys with XLAS showed more typical pathological performance than the girls. Patients with severe mutation were more likely to have proteinuria and hearing impairment. Renal pathology combined with NSG is an important means of diagnosis of AS.

A monocenter study on pediatric Alport syndrome featuring nephrotic syndrome as the primary manifestation

“…Recently, an increasing number of studies have reported gene mutations that causing AS in patients with both steroid-resistant NS and FSGS [12]. In cases where AS coexists with other kidney diseases, patients are prone to misdiagnosis, often as NS, IgA nephropathy, Henoch-Schönlein purpura nephritis, or thin basement membrane nephropathy [9].Clinically, some children with AS may have proteinuria as the initial clinical symptom, but the diagnosis of NS in AS patients is indeed rare. In this study, all 7 AS patients had the disease onset during school age, with NS as the primary clinical manifestation.…”

“…Variant loci were graded for pathogenicity according to the ACMG guidelines [8]. The mutations were classi ed as missense or severe mutations (large deletions, nonsense changes, mutations at the splice donor or acceptor site, and frameshift mutations) [9].…”