Аннотация
TBMD is a frequent nephropathy in some series, but the clinical significance of this diagnosis is still controversial, mainly regarding its relationship with Alport syndrome (ATS) and its long-term prognosis.This study analyses the clinical picture, histological findings and the results of familial and genetic investigations in 51 patients (18M, 33F) with a morphological diagnosis of TBMD established by EM, IF, and LM.They all had hematuria (macroscopic in 11) and 27 mild proteinuria, generally lower than 0.5 g/day.30 of them (60%) had a positive family history for hematuria; in 9 families cases with CRF ascribed to various nephropathies were found.Global sclerosis involving 5-15% of glomeruli was observed in 7 biopsies (14%).By immunohistochemistry IgA deposits were detected by IF in 4 cases and confirmed by EM in 3. Normal staining for type IV collagen a-chains was observed in all but one patient where a5(IV) was absent.In this patient molecular genetic analysis revealed a COL4A5 mutation.A COL4A3 mutation was detected in 2 additional pts.8 out of 38 patients followed for 12-240 months showed signs of disease progression or hypertension.Abnormalities of the gene encoding for collagen IV chains were detected in two of them.These observations confirm that TBMD is an heterogeneic but not always benign disorder and suggest that this diagnosis should prompt appropriate immunohistologic, familial and genetic investigations to identify early ATS cases and patients at risk of progression requiring an extended follow-up.