A case of STEC-negative hemolytic uremic syndrome with C2 gene mutation variant

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. While Shiga toxin-producing E. coli (STEC) remains the most common cause, atypical HUS (aHUS), driven by complement dysregulation, poses a significant diagnostic challenge, particularly in adults. We present the case of a 29-year-old female with no prior medical history who developed severe gastrointestinal symptoms, acute kidney injury, thrombocytopenia, and hemolytic anemia following suspected foodborne illness. Initial labs revealed schistocytosis, elevated LDH, low haptoglobin, and markedly impaired renal function. Given her high PLASMIC score (6), empiric plasmapheresis was initiated while awaiting ADAMTS13 results, which later returned normal. Despite negative testing for STEC, influenza, and other infectious etiologies, complement levels were borderline low, raising suspicion for aHUS. Although genetic testing revealed an equivocal C2 gene variant and common CFH polymorphisms statistically enriched in aHUS, the variant was classified as likely benign. The patient’s renal function improved significantly with supportive care and temporary hemodialysis, and ravulizumab was deferred. This case highlights the importance of early recognition and management of thrombotic microangiopathies, especially when infectious workup is negative and ADAMTS13 results are pending. Prompt initiation of plasmapheresis in cases with high PLASMIC scores remains critical, even in indeterminate presentations. Further investigation into the potential pathogenic role of rare complement gene variants such as C2 may refine our understanding of aHUS. This case underscores the need for rapid diagnostics and early resource mobilization in patients with suspected microangiopathic processes.