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Case Reports
. 2020 Mar 12;21(1):96.
doi: 10.1186/s12882-020-01748-2.

Cobalamin c deficiency associated with antifactor h antibody-associated hemolytic uremic syndrome in a young adult

C Philipponnet  1 , J Desenclos  2 , M Brailova  3 , J Aniort  2 , J L Kemeny  4 , C Deville  2 , V Fremeaux-Bacchi  5 , B Souweine  6 , A E Heng  2
Affiliations
Case Reports

Cobalamin c deficiency associated with antifactor h antibody-associated hemolytic uremic syndrome in a young adult

C Philipponnet et al. BMC Nephrol. .

Abstract

Background: Thrombotic microangiopathy (TMA) syndromes are characterized by the association of hemolytic anemia, thrombocytopenia and organ injury due to arteriolar and capillary thrombosis.

Case presentation: We report the first case of adult onset cobalamin C (Cbl C) 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 plasma exchanges were started in emergency. Exhaustive analyses showed 1) circulating anti factor H antibody and 2) hyperhomocysteinemia, hypomethioninemia and high levels of methylmalonic aciduria pointing towards Clb C disease. Cbl C disease has been confirmed by methylmalonic aciduria and homocystinuria type C protein gene sequencing revealing two heterozygous pathogenic variants. The kidney biopsy showed 1) intraglomerular and intravascular thrombi 2) noticeable thickening of the capillary wall with a duplication aspect of the glomerular basement membrane and a glomerular capillary wall IgM associated with Cbl C disease related TMA. We initiated treatment including hydroxycobalamin, folinic acid, betaine and levocarnitine and Eculizumab. Rituximab infusions were performed allowing a high decrease in anti-factor H antibody rate. Six month after the disease onset, Eculizumab was weaning and vitaminotherapy continued. Outcome was favorable with a dramatic improvement in kidney function.

Conclusion: TMA with renal involvement can have a complex combination of risk factors including anti-FH autoantibody in the presence of cblC deficiency.

Keywords: Anti-factor H antibody; Atypical hemolytic uremic syndrome; Cobalamin C (Cbl C) disease; Thrombotic microangiopathy.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Kidney histology. a Light microscopy, Masson’s trichrome staining, × 40. There was a diffuse augmentation of mesangial material and mesangial hypercellularity in all glomeruli, and a thickening of the glomerular basement membranes. Thrombi were present in the intraglomerular capillaries and in vessels of the intra juxtaglomerular apparatus. b Light microscopy, silver staining, × 60. Thickening of the capillary wall with a duplication aspect of the glomerular basement membrane. c Light microscopy, silver staining, × 40. Thrombi were present in vessels of the intra juxtaglomerular apparatus and in the arterioles. d Immunofluorescence, IgM staining, × 60. Mild glomerular capillary wall IgM deposits
Fig. 2
Fig. 2
Patient outcome
See this image and copyright information in PMC

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