A South African case study of familial membranoproliferative glomerulonephritis

Abstract

Membranoproliferative glomerulonephritis (MPGN) is an immune-mediated disease that is characterised by mesangial hypercellularity and endocapilliary proliferation with capillary wall remodeling which results in thickening of the glomerular basement membrane. (1) MPGN was traditionally classified on electron microscopy findings into MPGN type I, II, and III. Multiple genetic risk factors have been identified for MPGN II now referred to as dense deposit disease; however, relatively little is known regarding genetic risk factors for MPGN type I and III. A reclassification scheme that better reflects the pathophysiology of MPGN has been implemented. This scheme divides MPGN into immune-complex-mediated and complement-mediated MPGN. Previous descriptions of familial MPGN suggest that this entity falls within the category of complement-mediated MPGN. We describe a South African family with four family members affected with immune-complex-mediated MPGN. All other asymptomatic contactable family members were tested for proteinuria and haematuria and a pedigree for the family was established with an autosomal recessive with incomplete penetrance inheritance pattern or a multigenic inheritance pattern. A systematic review was then performed using the search terms of "inherited MPGN" and "Familial MPGN". In the systematic review of familial MPGN from 1981-2014, nine reports containing twelve families were reviewed totaling thirteen families including the South African family. Six families were found to have immune-complex-mediated MPGN iii and five families had complement-mediated MPGN. The data of two families was limited and thus couldn’t be reclassified.