Cobalamin C deficiency associated with anti-factor H antibody in young adult

Abstract

Thrombotic microangiopathy (TMA) is a life-threatening condition and involve emergency care. We report the first case of adult onset cobalamin C (CblC) disease associated with anti-factor H antibody-associated hemolytic uremic syndrome (HUS). A 19-year-old woman was admitted to the nephrology department owing to acute kidney failure, proteinuria, and hemolytic anemia with schizocytes. TMA was diagnosed and motivated plasma exchanges in emergency. Exhaustive analyses showed: – circulating anti-factor H antibody without the homozygous CFHR1-CFHR3 deletion that might contribute to hyperactivation of the alternative pathway of complement; – hyperhomocysteinemia, hypomethioninemia and high levels of methylmalonic aciduria pointing towards ClbC disease which has been confirmed by MMACHC gene sequencing revealing two heterozygous pathogenic variants. The kidney biopsy showed typical renal lesions in TMA with intraglomerular and intravascular thrombi. However, a noticeable thickening of the capillary wall with a duplication aspect of the glomerular basement membrane and a mild glomerular capillary wall IgM in immunofluorescence were noted and are associated with CblC disease related TMA. We initiated treatment including hydroxycobalamin, folinic acid, betaine and levocarnitine for CblC disease and Eculizumab. Rituximab infusions were performed allowing a high decrease in anti-factor H antibody rate. Six months after the disease onset, Eculizumab was weaning and vitaminotherapy continued. Outcome was favorable with a dramatic improvement in kidney function and no hemolysis stigma (Fig. 1). Cb1 C deficiency is a cause of microangiopathy even in the young adult and can be revealed by an isolated renal manifestation. A simple treatment introduced early in the disease's development allows recovery of the renal function. A specific patter on the renal histology with vacuolated aspect of the glomerular basement membrane and glomerular capillary wall IgM must motivate the research of cobalamin deficiency. The alternative complement pathway abnormalities might contribute to the TMA lesions and should be screen in patients with Cb1 C deficiency.