Hereditary atypical hemolytic uremic syndrome (aHUS), a dramatic disease frequently leading to dialysis, is associated with germline mutations of the CFH, CD46, or CFI genes.
In conclusion, we describe for the first time a disease-free individual with complete CD46 deficiency, confirming the extremely variable penetrance and genetic complexity of aHUS.
Recently, mutations and polymorphisms in complement regulator molecules FH and MCP but also in FI have been associated with atypical hemolytic uremic syndrome (aHUS).
Mutations in complement factor H (CFH), factor I (CFI), factor B (CFB), thrombomodulin (THBD), C3 and membrane cofactor protein (MCP), and autoantibodies against factor H (αFH) with or without a homozygous deletion in CFH-related protein 1 and 3 (∆CFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS).
Mutations in proteins that regulate complement (factor H, factor I, MCP/CD46, thrombomodulin) or promote (C3, factor B) amplification of its alternative pathway or anti-factor H antibodies predispose to aHUS.
We present a case of chronic thrombotic microangiopathy (TMA) after kidney transplantation in a recipient who had been classified as hypertensive ESRD and found to have a genetic defect in CD46, a transmembrane protein that regulates complement activation, indicating atypical hemolytic uremic syndrome (HUS).