Thrombotic microangiopathy (TMA) syndromes are characterized by the association of hemolytic anemia, thrombocytopenia and organ injury due to arteriolar and capillary thrombosis. 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. TMA with renal involvement can have a complex combination of risk factors including anti-FH autoantibody in the presence of cblC deficiency.

中文翻译：

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钴胺素c缺乏症与年轻成人中的抗因子h抗体相关的溶血性尿毒症综合征相关。

血栓性微血管病（TMA）综合征的特征是溶血性贫血，血小板减少症和由于小动脉和毛细血管血栓形成引起的器官损伤的关联。我们报告与抗因子H抗体相关的溶血性尿毒症综合征（HUS）相关的成人发作钴胺素C（Cbl C）疾病的第一例。一名19岁的妇女因急性肾衰竭，蛋白尿和精神分裂症引起的溶血性贫血而被录入肾脏病科。诊断为TMA，紧急情况下开始血浆置换。详尽的分析表明：1）循环抗H因子抗体和2）高同型半胱氨酸血症，低甲硫氨酸血症和高水平的甲基丙二酸尿症，提示Clb C病。已通过甲基丙二酸尿症和高半胱氨酸尿症的C型蛋白基因测序证实了Cbl C病，揭示了两个杂合的致病变异。肾脏活检显示1）肾小球内和血管内血栓形成2）毛细血管壁明显增厚，肾小球基底膜和与Cbl C疾病相关的TMA相关的肾小球毛细血管壁IgM重复。我们开始治疗，包括羟基钴胺素，亚叶酸，甜菜碱和左卡尼汀和依库丽单抗。进行利妥昔单抗输注可以大大降低抗因子H抗体的发生率。疾病发作六个月后，依库丽单抗断奶，继续进行维生素治疗。肾功能显着改善，预后良好。