Familial nephropathy differing from minimal change nephropathy and focal glomerulosclerosis

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 efface ment. Familial presentation is rare and mainly restricted to one generation . Methods. We describe the occurrence of a familiar nephropathy in a mother a nd two daughters. An initial diagnosis of minimal change nephropathy was ma de, but subsequently unique features became apparent. During follow-up. det ailed studies of renal function and urinary protein excretion were performe d. Available frozen renal biopsy material was revised and processed for imm unofluorescence to detect abnormalities in the expression of heparan sulfat e proteoglycans. The latter results were compared with renal biopsies of a control group composed of five adult patients with minimal change nephropat hy. Results. The mother and two daughters were proteinuric since their early ch ildhood. 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 patie nts retained normal renal function during follow-up. Detailed measurements revealed that the proteinuria was incredibly selective (selectivity index s imilar to0.01), and there was no evidence of tubulointerstitial damage, as reflected by a normal excretion of the low-molecular weight proteins beta ( 2)-microglobulin and alpha (1)-microglobulin. Renal biopsy performed in the mother and one daughter was thought to be compatible with minimal change n ephropathy. However. histologically;, two remarkable findings were made. By electron microscopy. there was no evidence of foot process retraction: spe cifically, the foot process width and slit pore diameter were normal. Furth ermore, in contrast to the control patients, the expression of heparan sulf ate polysaccharide side chains, as reflected by the staining with monoclona l antibody JM403, was normal. Conclusions. We propose that this family represents a new familial nephropa thy. The molecular basis of the permeability defect remains to be identifie d.