Alport syndrome: Expanding diagnosis and treatment

Alport syndrome (AS) is the second common monogenic cause of end-stage kidney disease (ESKD) worldwide and is caused by defective type 4 collagen due to pathogenic variants of COL4A3, COL4A4, or COL4A5. Type 4 collagen also exists in the eyes and ears, and thus ocular defects and hearing loss occur...

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Main Authors: Hou-Xuan Huang, I-Jung Tsai, Larry A. Greenbaum
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Pediatrics and Neonatology
Online Access:http://www.sciencedirect.com/science/article/pii/S1875957224001918
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author Hou-Xuan Huang
I-Jung Tsai
Larry A. Greenbaum
author_facet Hou-Xuan Huang
I-Jung Tsai
Larry A. Greenbaum
author_sort Hou-Xuan Huang
collection DOAJ
description Alport syndrome (AS) is the second common monogenic cause of end-stage kidney disease (ESKD) worldwide and is caused by defective type 4 collagen due to pathogenic variants of COL4A3, COL4A4, or COL4A5. Type 4 collagen also exists in the eyes and ears, and thus ocular defects and hearing loss occur in AS. The understanding of AS has expanded over the past two decades due to greater availability of genetic testing and research on genotype-phenotype correlation. Patients previously diagnosed with idiopathic steroid resistant nephrotic syndrome or ESKD of unknown etiology may now be diagnosed as AS if pathogenic COL4A3-5 variants are identified. Some carriers of heterozygous COL4A3-5 variants may now be classified into females with X-linked AS or autosomal dominant AS, if there are typical pathologic changes in the glomerular basement membrane or if there is proteinuria and progression of kidney disease. Lastly, it has been recommended that renin-angiotensin-aldosterone system inhibition be started as soon as possible for selected AS patients for its long-term protective effect against kidney function deterioration. The purpose of this review is to introduce these important concepts to general pediatricians and pediatric nephrologists.
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spelling doaj-art-813b17f008d643dc887b2e9adbee16bf2025-08-20T02:43:29ZengElsevierPediatrics and Neonatology1875-95722025-02-0166S13S1710.1016/j.pedneo.2024.10.005Alport syndrome: Expanding diagnosis and treatmentHou-Xuan Huang0I-Jung Tsai1Larry A. Greenbaum2Department of Pediatrics, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pediatrics, National Taiwan University Hospital, Taipei, TaiwanEmory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia; Corresponding author. 2174 North Druid Hills Road NE, Atlanta, 30329, Georgia.Alport syndrome (AS) is the second common monogenic cause of end-stage kidney disease (ESKD) worldwide and is caused by defective type 4 collagen due to pathogenic variants of COL4A3, COL4A4, or COL4A5. Type 4 collagen also exists in the eyes and ears, and thus ocular defects and hearing loss occur in AS. The understanding of AS has expanded over the past two decades due to greater availability of genetic testing and research on genotype-phenotype correlation. Patients previously diagnosed with idiopathic steroid resistant nephrotic syndrome or ESKD of unknown etiology may now be diagnosed as AS if pathogenic COL4A3-5 variants are identified. Some carriers of heterozygous COL4A3-5 variants may now be classified into females with X-linked AS or autosomal dominant AS, if there are typical pathologic changes in the glomerular basement membrane or if there is proteinuria and progression of kidney disease. Lastly, it has been recommended that renin-angiotensin-aldosterone system inhibition be started as soon as possible for selected AS patients for its long-term protective effect against kidney function deterioration. The purpose of this review is to introduce these important concepts to general pediatricians and pediatric nephrologists.http://www.sciencedirect.com/science/article/pii/S1875957224001918
spellingShingle Hou-Xuan Huang
I-Jung Tsai
Larry A. Greenbaum
Alport syndrome: Expanding diagnosis and treatment
Pediatrics and Neonatology
title Alport syndrome: Expanding diagnosis and treatment
title_full Alport syndrome: Expanding diagnosis and treatment
title_fullStr Alport syndrome: Expanding diagnosis and treatment
title_full_unstemmed Alport syndrome: Expanding diagnosis and treatment
title_short Alport syndrome: Expanding diagnosis and treatment
title_sort alport syndrome expanding diagnosis and treatment
url http://www.sciencedirect.com/science/article/pii/S1875957224001918
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AT ijungtsai alportsyndromeexpandingdiagnosisandtreatment
AT larryagreenbaum alportsyndromeexpandingdiagnosisandtreatment