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).
Recurrent atypical haemolytic uraemic syndrome post kidney transplant due to a CD46 mutation in the setting of SMARCAL1-mediated inherited kidney disease.
In summary, these data suggest that genotyping for the risk haplotypes in CFH and MCP may help predict the risk of developing aHUS in unaffected carriers of mutations.
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 presented the second reported case of aHUS associated with a heterozygous c.191G > T mutation in exon 2 of MCP who responded rapidly to plasma exchange.
We describe a case of a 22-year-old man who presented with clinical features of atypical haemolytic uraemic syndrome and in whom genetic analysis of complement regulatory proteins demonstrated a CD46 mutation.
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).
In this individual, the development of aHUS has been facilitated by the combination of a trigger (pregnancy), an acquired rare genetic variant (CFH mutation) and a common susceptibility factor (CD46 haplotype).
Furthermore, we found weak indications that there is one protective and one risk haplotype predisposing to nephritis composed of several polymorphisms in noncoding regions of CD46, which were previously implicated in aHUS.
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.