atypical HUS

Atypical haemolytic uremic syndrome (atypical HUS) is an ultra-rare, potentially life-threatening, genetic disease that leads to the formation of blood clots in small blood vessels throughout the body.1,2 These blood clots can lead to stroke, heart attack, kidney failure and death.

Atypical HUS is caused by a permanent genetic mutation that leads to uncontrolled and excessive activation of complement.3 In healthy individuals, complement is used to attack foreign particles; in patients with atypical HUS, the body is unable to control the activation of complement. As a result, patients with atypical HUS face a lifelong risk of sudden, potentially catastrophic, and life-threatening complications that can occur throughout the body and affect vital organs, including the kidneys, heart and brain. 1,3,4,5,6

Atypical HUS can be difficult to diagnose because the disease is so rare that many doctors have never encountered a case of it, or may not recognise it. Initial signs and symptoms of atypical HUS include confusion, stomach pain, vomiting, and diarrhoea. atypical HUS affects both adults and children. In a large group of atypical HUS patients, about 50 percent were diagnosed under the age of 18.6 Among paediatric patients, atypical HUS can cause stroke, heart attacks, seizures and high blood pressure.7 One of the most common signs of atypical HUS is kidney failure. Seventy-nine percent of all patients with atypical HUS die, require kidney dialysis or have permanent kidney damage within three years after diagnosis despite plasma exchange or plasma infusion (PE/PI).6 Moreover, 33 to 40 percent of patients die or progress to end-stage renal disease with the first clinical manifestation of atypical HUS despite PE/PI.4,6

1. Loirat C, Noris M, Fremeaux-Bacchi V. Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2008;23:1957-1972.
2. Hosler GA, Cusumano AM, Hutchins GM. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are distinct pathologic entities: a review of 56 autopsy cases. Arch Pathol Lab Med. 2003;127:834-839.
3. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361:1676-1687.
4. Caprioli J, Noris M, Brioschi S, et al; for the International Registry of Recurrent and Familial HUS/TTP. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108:1267-1279.
5. Hirt-Minkowski P, Dickenmann M, Schifferli JA. Atypical hemolytic uremic syndrome: update on the complement system and what is new. Nephron Clin Pract. 2010;114:c219-c235.
6. Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and familial atypical HUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5:1844-1859.
7. Neuhaus TJ, Calonder S, Leumann EP. Heterogeneity of atypical haemolytic uraemic syndromes. Arch Dis Child. 1997;76:518-521.