Thin basement membrane disease and autosomal dominant Alport syndrome are a unity of opposites. Modern ideas and unsolved problems

Thin basement membrane disease (TBMD) and autosomal dominant Alport syndrome (ADAS) are inherited renal diseases caused by structural abnormalities of α-3 and α-4 chains of collagen type 4. The concept that TBMD and ADAS are distinct conditions was initially proposed based on supposed clinical and morphologic differences. Most patients with TBMD have hematuria with little or no proteinuria, normal renal function, and diffuse thinning of the glomerular basement membrane (GBM) on electron microscopy. However, there are patients with TBMD who develop end-stage chronic kidney disease (ESKD) in adulthood. In contrast, Alport syndrome (AS) is defined as progressive nephropathy accompanied by hearing loss and ocular abnormalities, with irregular thickening and lamellation of the GBM. However, many patients with ADAS have no extrarenal manifestations, ESKD does not develop until old age, and the only change in the GBM is thinning. Genetic studies have proven that both TBMD and ADAS are caused by heterozygous pathogenic variants in the COL4A3 and COL4A4 genes. There are difficulties in differentiating between these two conditions and the old concept of two different diseases should be reconsidered. The diagnosis of AS is important because it facilitates close follow-up and early treatment of patients, whereas the diagnosis of TBMD may lead to an underestimation of the risk of developing ESKD. Although ADAS has long been considered an extremely rare condition, recent studies using next-generation sequencing have demonstrated that the number of these patients is much larger than previously thought, leading to much debate over the diagnosis of this condition. We present a review of available publications on TBMD and ADAS and our clinical observation demonstrating the difficulties encountered in diagnosing collagen type 4 pathology.

заболевание тонкой базальной мембраны, аутосомно-доминантный синдром Альпорта, гетерозиготный вариант COL4A3 или COL4A4, thin basement membrane disease, autosomal dominant Alport syndrome, heterozygous COL4A3 or COL4A4 variant

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