Factor H deficiency and renal involvement.

Factor H is a regulatory protein of the alternate complement activation pat hway. Factor H deficiency manifesting as permanent alternate pathway activa tion has been reported in patients with hemolytic uremic syndrome (HUS), co llagen III glomerulopathy, IgA nephropathy, systemic lupus erythematosus wi th C2 deficiency, and membranoproliferative glomerulonephritis. Six pediatr ic cases of factor H deficiency are reviewed. Three (cases 1-3), all boys, presented with atypical HUS characterized by hemolytic anemia, severe hyper tension, and progression to end-stage renal failure. Recurrent infections o ccurred in cases 1 and 2, both of whom had repeatedly low factor H levels w ith low C3 levels. Case 3 had C3 levels in the low-to-normal range and norm al factor H levels with reduced factor H activity. Cases 4 and 5 were broth ers born to consanguineous parents and presented with recurrent macroscopic hematuria in the absence of significant proteinuria or renal function impa irment. Renal biopsy demonstrated mesangial proliferation with dense C3 dep osits in both cases. Case 6 was a 12-month-old girl presenting with macrosc opic hematuria, nephrotic syndrome, anemia, and glomerular filtration rate (GFR) reduction. Renal biopsy demonstrated proliferative crescentic glomeru lonephritis with C3 deposits. Following a course of steroid therapy, protei nuria decreased and both GFR and factor I-I returned to normal. These six c ases illustrate the diversity of clinical and histological manifestations s een in factor H-deficient patients. The exact pathogenic role of factor I-I deficiency remains to be determined.