A COL4A5 mutation with glomerular disease and signs of chronic thrombotic microangiopathy
Morphological study of the kidney is generally the first step in the diagnosis of Alport's syndrome. Light microscopy study allows to suggest the diagnosis with the association of focal and segmental glomerulosclerosis, GBM anomalies when studied with silver staining, interstitial foam cells, and negative standard immunofluorescence study. GBM anomalies observed by electron microscopy are nearly specific with thickening splitting and fragmenting of the lamina densa. GBM anomalies are the consequence of a collagen IV disease. Thus, immunohistochemical results obtained with 6 different alpha(IV) are essential and allow to evaluate the mode of inheritance. Schematically, in the X dominant AS form, GBM, distal tubular BM and collecting duct BM do not express alpha3/alpha4, alpha5(IV). In the autosomic recessive AS form, collecting duct BM alone express alpha5(IV) without expression of alpha3(IV) and alpha5(IV) chains along the GBM and distal TBM.