Loss of regulation leads to unchecked C3bBb activity, generating C3a (anaphylatoxin) and C3b, which deposits on glomerular endothelial cells. This triggers:
aHUS has an estimated incidence of 0.5–1 per million per year, accounting for approximately 5–10% of all pediatric HUS cases but a higher proportion of adult cases. Without treatment, up to 50% of patients progress to end-stage renal disease (ESRD) or die during the first acute episode. The advent of complement-blocking monoclonal antibodies has transformed aHUS from a disease with guarded prognosis to a manageable chronic condition, yet challenges in diagnosis, cost, and long-term monitoring persist. atypical hemolytic syndrome
Complications of aHUS can include:
The hemolytic uremic syndrome (HUS) was first described by Conrad Gasser in 1955. For decades, the term HUS was almost synonymous with diarrheal illness caused by Shiga-toxin-producing E. coli . However, it became evident that a subset of patients—often with a relapsing course, familial clustering, or poor response to supportive care—had a distinct pathophysiology. This variant, now known as atypical HUS (aHUS), represents a disorder of complement dysregulation. Loss of regulation leads to unchecked C3bBb activity,
More than 60% of aHUS patients harbor rare genetic variants in complement genes, though penetrance is incomplete (often ~50%), indicating that a "second hit" (e.g., infection, pregnancy, surgery) is required for disease expression. though penetrance is incomplete (often ~50%)