Atypical Hemolytic Syndrome ~repack~ 🎯 Limited

| Gene | Protein | Function | % of aHUS | Risk of ESRD without treatment | Recurrence post-transplant | |------|---------|----------|------------|-------------------------------|----------------------------| | CFH | Factor H | Cofactor for FI, decays C3bBb | 20-30% | 70-80% | Very high (>70%) | | MCP | CD46 | Cofactor for FI on cell surface | 10-15% | 30-40% | Low (if kidney alone) | | CFI | Factor I | Cleaves C3b and C4b | 5-10% | 60% | High | | C3 | C3 | Convertase component | 5-10% | 60-70% | High | | CFB | Factor B | Convertase component (gain-of-function) | 1-2% | High | High | | THBD | Thrombomodulin | Enhances FI activation | ~5% | Intermediate | Unknown |

aHUS, complement, thrombotic microangiopathy, eculizumab, factor H, membrane cofactor protein, ravulizumab. 1. Introduction 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.

Author: [Generated for Academic Use] Date: April 13, 2026 Abstract Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Unlike typical Shiga-toxin producing E. coli HUS (STEC-HUS), aHUS results from chronic, uncontrolled activation of the alternative complement pathway. This paper provides a comprehensive review of the genetic and acquired abnormalities leading to endothelial injury, the clinical spectrum from infancy to adulthood, diagnostic challenges in distinguishing aHUS from other TMAs, and the paradigm shift from plasma exchange to terminal complement inhibition with eculizumab and ravulizumab. We also explore emerging therapies targeting proximal complement components and the ongoing challenge of long-term management and transplantation.