title: H deficiency in two brothers with atypical dense intramembranous deposit disease.
abstract: We report an H deficiency in two Algerian brothers who had early-onset glomerulonephritis. In addition, one suffered from serious lung infections. The H deficiency was defined by undetectable CH50 and AP50, and low levels of H, C3 and B (less than 10% of normal levels). I and classical pathway components, including C4-bp were normal. CR1 was present on both patients' erythrocytes. No nephritic factor or other circulating alternative pathway activator was detected. The parents, who are first cousins, and a healthy brother and sister had half-normal levels of H. These findings favor an autosomal recessive transmission of the H defect. Although by electron microscopy renal biopsies from both patients were typical for dense intramembranous deposit disease, immunofluorescence microscopy showed an atypical pattern with abundant granular C3 deposits within the mesangium and along the capillary walls. Alternative pathway activators, possibly related to dense deposits, may allow the formation of membrane-associated C3/C5 convertases, unusually stable in the absence of H, since C5, C6, C7, C8 and C9 levels were decreased in both patients. This observation may represent an interesting clue to the relationship between nephritic factor, alternative pathway activation, and dense intramembranous deposit disease.
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000172:deficiency*; D017242:Complement Factor H; D003170:Complement Pathway, Alternative; D005921:Glomerulonephritis / Q000097:blood* / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D010375:Pedigree
chemical_list: C493495:CFH protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H