HYPOCOMPLEMENTEMIC AUTOSOMAL RECESSIVE HEMOLYTIC-UREMIC SYNDROME WITHDECREASED FACTOR-H - ORIGINAL ARTICLE

We describe the clinical course, complement components, and pathologic al findings of 10 infants with autosomal recessive hemolytic uremic sy ndrome (HUS). All patients were members of one extended highly inbred Bedouin kindred. The median age of presentation was 2 weeks (range 1-2 0 weeks). Eight patients died, 2 patients are alive, on dialysis. Rena l biopsies revealed thrombotic microangiopathy with a predominant earl y arteriolar involvement and subsequent development of ischemic glomer ular changes. Immunofluorescence was positive for C3 in glomeruli. All patients had low complement components levels during and between rela pses, and in some this was evident soon after birth and prior to the o nset of symptoms. This deficiency could not be normalized by repeated plasma transfusions. Biosynthetic labelling of patients' fibroblasts d emonstrated normal rates of C3 protein synthesis. Serum factor H level s were greatly decreased or absent in 4 patients tested and moderately decreased in 15 of 23 healthy unaffected siblings and patients. This defect may cause complement activation and consumption, possibly at th e endothelial cell level.