Familial "full house" nephropathy with classical complement pathway dysregulation

Introduction: Full house nephropathy (FHN) is reported when glomerulonephritis with numerous immune deposits is seen in kidney biopsy, but systemic lupus erythematosus (SLE) cannot be diagnosed. Familial SLE has been previously reported, but almost no reports exist on familial FHN.

Cases description: Two brothers of non-consanguineous parents developed childhood steroid resistant nephrotic syndrome, in association with decreased serum levels of some of the components of the classical complement system (C1q and C2) and a FHN pattern on kidney biopsy, with subepithelial deposits but no additional criteria for SLE. One of the siblings had also a tendency for invasive bacterial infections. Treatment with mycophenolate mofetil induced nephrotic syndrome remission, as well as normalization of the depressed complement components. Trio exome sequencing for one sibling and his parents was non-diagnostic.

Conclusion: This is the first description of familial FHN, in association with decreased classical complement system components and immune deficiency. Both patients responded to immunosuppression, suggesting a possible genetic tendency for autoantibody development, leading to complement dysregulation. This is similar to other diseases, such as AIRE mutations causing anti IL17 antibodies and candidiasis, and CFHRP mutations leading to anti factor H antibodies and atypical hemolytic uremic syndrome.