Differential diagnosis between X-linked Alport syndrome and thin basement membrane nephropathy

Abstract

To the Editor: We read with interest the editorial by Gregory1.Gregory M.C. Alport syndrome and thin basement membrane nephropathy: Unraveling the tangled strands of type IV collagen.Kidney Int. 2004; 65: 1109-1110Google Scholar to the article “COL4A3 mutations and their clinical consequences in thin basement membrane nephropathy (TBMN).” Correctly, the necessity is stressed to clearly distinguish thin basement membrane nephropathy (TBMN) from Alport syndrome (AS), especially when the family history of renal failure and deafness is lacking. We believe that some complementary information should be given. When renal biopsy is not typical [only thin glomerular basement membrane (GBM)], the immunohistochemistry evaluation for α(IV) chains in the GBM can easily distinguish TBMN from Alport syndrome because in the latter α3/α4/α5 chains are abnormally distributed or even absent2.Kashtan C.E. Alport syndrome and thin glomerular basement membrane disease.J Am Soc Nephrol. 1998; 9: 1736-1750Google Scholar, 3.Rizzoni G. Massella L. Muda A.O. Alpha 5 COLIV chain distribution in glomerular basement membrane in a male with X-linked Alport syndrome and thin basement membrane.Pediatr Nephrol. 2000; 15: 325Google Scholar. In addition, the use of skin biopsy has been demonstrated to be a very useful tool for diagnosing X-linked AS. The reliability of skin immunohistochemistry for diagnosis of X-linked AS has been estimated in about 80% in affected males and is a smaller percentage in female carriers4.Kashtan, CE: Uptodate, 2003Google Scholar. Very recently, the use of confocal laser microscopy in the examination of the epidermal basement membrane (EBM) had been proven to be able to detect α5(IV) chain altered distribution in a much higher proportion of patients with X-linked AS5.Onetti Muda A. Massella L. Giannakakis K. et al.confocal microscopy of the skin in the diagnosis of x-linked alport syndrome.J Invest Dermatol. 2003; 121: 208-211Google Scholar. It is our experience that skin biopsy, examined with conventional, and if needed, with confocal microscopy, is able to virtually detect (almost) all cases of X-linked AS5.Onetti Muda A. Massella L. Giannakakis K. et al.confocal microscopy of the skin in the diagnosis of x-linked alport syndrome.J Invest Dermatol. 2003; 121: 208-211Google Scholar, thus allowing to avoid or to postpone more invasive and/or expensive diagnostic procedure like renal biopsy and genetic investigations, which, in addition, are not diagnostic in all cases.