MORPHOLOGICAL ASPECTS OF ALPORT'S SYNDROME

M. Šćukanec-Špoljar, I. Ilić

Alport's syndrome (AS) is an inherited disorder of glomerular basement membrane (GBM) characterised by hematuria, progressive renal failure, sensorineural hearing loss and some ocular anomalies. Histological features as well as immunofluorescence are quite unspecific. However, electron microscopy shows very characteristic alternations of GBM including GBM thickening with splitting and lamellation of lamina densa which alternates with segments of extreme thinning of GBM. In young children, such extreme GBM thinning can be widespread as in thin GBM disease with benign familial hematuria. GBM alternations, however, are not pathognomonic since they can be rarely seen in various other glomerulopathies. Diagnostic problems arise in the cases with diffuse GBM thinning as well as in those were specific EM alternations are found in children without any other sign of AS. In such situations, thorough clinical investigation and long-term surveillance are required. Recently the etiology of AS has been elucidated by discovery of 3 large genes coding for synthesis of 6 alpha chains of collagen IV (COL 4 alpha 1-6) which is the major component of basement membranes. Mutations of those genes result in abnormal alpha-chains that cannot bind specific monoclonal antibodies. Because of that, alpha 1-5 chain expression analysis in frozen tissue by in situ hybridisation or immunofluorescence, is considered today to be the best approach to the diagnosis of AS and to the determination of the mode of inheritance in each case. Genetic analysis of the locus of mutation is also possible, but it is time and money consuming and the results are obtained only in about 60% of cases. Another complication related to AS can occur after renal transplantation. Antibodies can be formed against normal alpha 5 chains of the graft which present as foreign to the host, with the consequence of anti-GBM glomerulonephritis.