The atypical human urolithiasis syndrome (aHUS) is a thrombotic microangiopathy characterized by the symptom complex thrombocytopenia, hemolytic anemia, and acute renal failure.
Compared to typical HUS, which occurs preferentially in childhood and due to bacterial toxins (Shigatoxin) in infections, v.a. with enterohumorrhagic E. coli (EHEC), Shigella or Salmonella, there is a lack of evidence for aHUS in the aHUS and haemorrhagic diarrhea.
Atypical HUS occurs in about 10% of HUS cases and has a worse prognosis than typical HUS. The cause is genetic, in 60-70% of patients mutations and genetic polymorphisms can be detected in complement genes. The genetic changes affect both the complement regulators factor H, factor I, membrane factor protein and thrombomodulin as well as the components of the central C3 convertase C3 and factor B. They are associated with uncontrolled activation of the complement system.
Children, adolescents and adults alike may become ill with aHUS. Common causes include pregnancy, bone marrow or stem cell transplantation, immunosuppressants and other drugs, cancer, cocaine use, and systemic lupus erythematosus (SLE).
In about 50 percent of patients, aHUS leads to complete kidney failure requiring dialysis in a very short time. An important differential diagnosis for typical and atypical HUS is the thrombotic thrombocytopenic purpura (TTP). Therapeutically, plasmapheresis should be performed if there is a reasonable suspicion of atypical HUS. In addition, current studies have shown that eculizumab, a monoclonal antibody to complement factor C5, is a promising treatment option.