X-LINKED ALPORT-SYNDROME IN FEMALES

Alport syndrome (AS) is in the differential diagnosis of hematuria. Va riability in clinical presentation and in the ultrastructural changes of the glomerulus can make the diagnosis of AS a challenge in female p atients. The purpose of this report is to present immunostaining for g lomerular basement membrane (GBM) expression of alpha 5(IV) as an adju nctive diagnostic method. Renal biopsy specimens from eight female pat ients with clinical presentation suggestive of AS were studied. The pa tients were between 7 and 36 years of age; six were between 12 and 15 years. Light microscopy and immunohistochemistry using a monoclonal an tibody to alpha 5(IV) were performed. Controls showed a continuous lin ear pattern along the GEM in normal kidneys and absence in renal biops y specimens from male X-linked AS patients. To express the variability of the ultrastructural GEM changes among the patients in the series, we developed a semiquantitative Alport Index, obtained by quantificati on of severity and extent of ultrastructural GEM changes. With immunoh istochemistry, we showed an interrupted, discontinuous linear pattern for alpha 5(IV) in glomeruli from the eight patients in the series, co nfirming the diagnosis of X-linked AS. The ultrastructutal Alport Inde x varied between 6 and 47, showing the heterogeneity in the severity o f the GEM changes, even among the six patients aged between 12 and 15 years. In three of the eight biopsy specimens, the predominant change was thin GEM, and the Alport Index was below 20. Immunohistochemistry for alpha 5(IV) in renal biopsy specimens can identify female patients heterozygous for X-linked AS. In this series, the method led to the d iagnosis of AS in female patients in whom the predominant ultrastructu ral change was thin basement membrane. Copyright (C) 1998 by W.B. Saun ders Company.