The variable course of women with X-linked Alport Syndrome

Abstract

X-linked Alport syndrome (XLAS) arises from mutations in the COL4A5 gene encoding the α5-chain of type IV collagen and is associated with hematuria, ocular abnormalities and high-tone sensorineural hearing loss. Nearly all affected males have decreased kidney function resulting in end-stage renal disease (ESRD) as early as the second decade of life. It was long thought that affected females had a benign outcome; however, in recent decades, it has become quite clear that they too are at risk for developing nephrotic syndrome, decreased kidney function and ESRD. We report two young females presenting with microscopic hematuria and proteinuria diagnosed with XLAS on renal biopsy. Both developed nephrotic-range proteinuria and progressive renal insufficiency. Additionally, both developed extra-renal manifestations of XLAS. The ultrastructural and immunofluorescence features on kidney biopsy were instrumental in making the diagnosis of heterozygous XLAS as neither patient had a family history of AS. © 2013 The Author.