OBSOLETE: Atypical hemolytic uremic syndrome with thrombomodulin anomaly

Atypical hemolytic uremic syndrome with thrombomodulin anomaly (aHUS due to THBD mutation) was previously classified as a distinct subtype of atypical hemolytic uremic syndrome (aHUS) caused by mutations in the THBD gene, which encodes thrombomodulin. This Orphanet entry (ORPHA:217023) is now marked as OBSOLETE, as the condition has been reclassified and merged into the broader category of atypical hemolytic uremic syndrome. Thrombomodulin is a glycoprotein expressed on endothelial cell surfaces that plays a role in regulating complement activation and coagulation. Mutations in THBD were found to impair complement regulation, contributing to the hallmark features of aHUS: thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The disease primarily affects the kidneys, blood, and vascular system. Patients typically present with hemolytic anemia (destruction of red blood cells), low platelet counts, and progressive renal failure. Episodes may be triggered by infections, pregnancy, or other complement-activating events. The condition can occur at any age but often presents in childhood. Treatment for aHUS, including cases associated with THBD mutations, has been transformed by the availability of complement inhibitor therapy (eculizumab and ravulizumab), which blocks terminal complement activation. Plasma exchange/infusion was historically used and may still be employed in acute settings. Supportive care including dialysis may be necessary during severe episodes. Because this entry is obsolete, patients and clinicians should refer to the broader aHUS classification for current management guidelines.

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