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A 18-year-old female patient with class IV lupus nephropathy, underwent unresponsive subsequent therapies with steroids, iv cyclophosphamide, rituximab and belimumab plus maintenance therapy with mycophenolate. She was finally started on chronic hemodialysis. Three years later she was admitted due to abdominal pain and gastrointestinal bleeding. A CT scan revealed micro-ulceration of the intestinal mucosa interpreted as lupus enteritis. The patient received treatment with corticosteroids and rituximab. One month later, she was readmitted with gastrointestinal bleeding and hemodynamic decompensation. A colonic mucosal biopsy was consistent with ischemic phenomena associated with thrombotic microangiopathy. Laboratory results were negative for peripheral hemolytic anemia; C3: 74 mg/dL (83-193 mg/dL), C4: 11 mg/dL (15-57 mg/dL). The previous kidney biopsies were reviewed for the search of thrombotic microangiopathy (TMA) but were non-contributory. Homocysteine level 68 µmol/L. She underwent daily plasmapheresis with plasma exchange, followed by eculizumab infusions, after which plasmapheresis was withheld, resulting in a significant clinical improvement. Genetic testing revealed an alteration in the MMACHC gene, a mutation associated with vitamin B12 deficiency and hyperhomocysteinemia. She was started on 5000µgr of vitamin B12, despite normal levels. Homocysteine levels decreased to 15 µmol/L, C3: 83mg/dL, C4: 17mg/dL, anti-DNA negative and anti-factor H antibodies were negative result. The genetic allelic study of MTHFR enzyme is being studied.
abstract
Lupus is a well-known cause of thrombotic microangiopathy and of secondary atypical hemolytic uremic syndrome (aHUS). A mutation associated with vitamin B12 and hyperhomocysteinemia could be an additional cause of endothelial damage and TMA. These findings could also partially explain the lack of response to the immunosuppressant regime for lupus nephritis. A mutation in the MMACHC gene as a cause of primary aHUS is to be determined.