Alport Syndrome and Alport Kidney Diseases - Elucidating the Disease Spectrum

Overview

Journal Curr Opin Nephrol Hypertens

Specialties Cardiology & Vascular Diseases
Nephrology

Date 2024 Mar 13

PMID 38477333

Authors

Pongpratch Puapatanakul

Jeffrey H Miner

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: With the latest classification, variants in three collagen IV genes, COL4A3 , COL4A4 , and COL4A5 , represent the most prevalent genetic kidney disease in humans, exhibiting diverse, complex, and inconsistent clinical manifestations. This review breaks down the disease spectrum and genotype-phenotype correlations of kidney diseases linked to genetic variants in these genes and distinguishes "classic" Alport syndrome (AS) from the less severe nonsyndromic genetically related nephropathies that we suggest be called "Alport kidney diseases".

Recent Findings: Several research studies have focused on the genotype-phenotype correlation under the latest classification scheme of AS. The historic diagnoses of "benign familial hematuria" and "thin basement membrane nephropathy" linked to heterozygous variants in COL4A3 or COL4A4 are suggested to be obsolete, but instead classified as autosomal AS by recent expert consensus due to a significant risk of disease progression.

Summary: The concept of Alport kidney disease extends beyond classic AS. Patients carrying pathogenic variants in any one of the COL4A3/A4/A5 genes can have variable phenotypes ranging from completely normal/clinically unrecognizable, hematuria without or with proteinuria, or progression to chronic kidney disease and kidney failure, depending on sex, genotype, and interplays of other genetic as well as environmental factors.

Citing Articles

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A Novel Loss-of-Function Variant in COL4A3 in a Consanguineous Moroccan Family Displaying the Alport Syndrome with Variable Clinical Expression.

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