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* Context.-Alport syndrome and thin glomerular basement membrane nephropathy (TBMN) are genetically heterogenous conditions characterized by structural abnormalities in the glomerular basement membrane and an initial presentation that usually involves hematuria. Approximately 40% of patients with TBMN are heterozygous carriers for autosomal recessive Alport syndrome, with mutations at the genetic locus encoding type IV collagen α^sub 3^ [α^sub 3^(IV)] and α^sub 4^ chains. However, although the clinical course of TBMN is usually benign, Alport syndrome, particularly the X-linked form with mutations in the locus encoding the α^sub 5^ chain of type IV collagen [α^sub 5^(IV)], typically results in end-stage renal disease. Electron microscopy is essential to diagnosis of TBMN and Alport syndrome on renal biopsy, although electron microscopy alone is of limited value in distinguishing between TBMN, the heterozygous carrier state of X-linked Alport syndrome, autosomal recessive Alport syndrome, and even early stages of X-linked Alport syndrome.
Objectives.-To review diagnostic pathologic features of each of the above conditions, emphasizing the need for immunohistology for α^sub 3^(IV) and α^sub 5^(IV) in addition to electron microscopy to resolve this differential diagnosis on a renal biopsy. The diagnostic value of immunofluorescence studies for α^sub 5^(IV) on a skin biopsy in family members of patients with Alport syndrome also is reviewed.
Data Sources.-Original and comprehensive review articles on the diagnosis of Alport syndrome andTBMN from the past 35 years, primarily the past 2 decades, and experience in our own renal pathology laboratory.
Conclusions.-Although Alport syndrome variants and TBMN do not show characteristic light microscopic findings and can be difficult to differentiate from each other even by electron microscopy, using a combination of electron microscopy and immunohistology for α^sub 3^(IV) and α^sub 5^(IV) enables pathologists to definitively diagnose these disorders on renal biopsy in most cases.
(Arch Pathol Lab Med. 2009;133:224-232)
Alport syndrome and thin glomerular basement membrane nephropathy (TBMN) are genetically heterogenous conditions characterized by structural abnormalities in the glomerular basement membrane (GBM). Both conditions typically present with hematuria, with the course of Alport syndrome usually manifested by increasing proteinuria and progressive renal insufficiency developing at varying ages, ranging from childhood to early or even middle-aged adulthood, although this age is fairly constant within affected members of the same family.1-3 Patients with Alport syndrome often, although not always,...