Abstract
BACKGROUND: Nephrotic syndrome in childhood is mainly due to minimal change nephropathy. In general, it is characterized by selective proteinuria, by steroid responsiveness, and histologically by podocytic foot process effacement. Familial presentation is rare and mainly restricted to one generation. METHODS: We describe the occurrence of a familial nephropathy in a mother and two daughters. An initial diagnosis of minimal change nephropathy was made, but subsequently unique features became apparent. During follow-up, detailed studies of renal function and urinary protein excretion were performed. Available frozen renal biopsy material was revised and processed for immunofluorescence to detect abnormalities in the expression of heparan sulfate proteoglycans. The latter results were compared with renal biopsies of a control group composed of five adult patients with minimal change nephropathy. RESULTS: The mother and two daughters were proteinuric since their early childhood. The mother revealed a persistent nephrotic syndrome for more than 20 years despite treatment with various immunosuppressive drugs. Likewise, treatment with prednisone was ineffective in the daughters. All three patients retained normal renal function during follow-up. Detailed measurements revealed that the proteinuria was incredibly selective (selectivity index approximately 0.01), and there was no evidence of tubulointerstitial damage, as reflected by a normal excretion of the low-molecular weight proteins beta(2)-microglobulin and alpha1-microglobulin. Renal biopsy performed in the mother and one daughter was thought to be compatible with minimal change nephropathy. However, histologically, two remarkable findings were made. By electron microscopy, there was no evidence of foot process retraction; specifically, the foot process width and slit pore diameter were normal. Furthermore, in contrast to the control patients, the expression of heparan sulfate polysaccharide side chains, as reflected by the staining with monoclonal antibody JM403, was normal. CONCLUSIONS: We propose that this family represents a new familial nephropathy. The molecular basis of the permeability defect remains to be identified.
