Typical hemolytic uremic syndrome (https://omim.org/entry/235400) is characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia associated with distorted erythrocytes (‘burr cells’). The vast majority of cases (90%) are sporadic, occur in children under 3 years of age, and are associated with epidemics of diarrhea caused by verotoxin-producing E. coli. The death rate is very low, about 30% of cases have renal sequelae, and there is usually no relapse of the disease. This form of HUS usually presents with a diarrhea prodrome (thus referred to as D+HUS) and has a good prognosis in most cases. In contrast, a subgroup of patients with HUS have an atypical presentation (aHUS or D-HUS) without a prodrome of enterocolitis and diarrhea and have a much poorer prognosis, with a tendency to relapse and frequent development of end-stage renal failure or death. These cases tend to be familial. Both autosomal recessive and autosomal dominant inheritance have been reported (Goodship et al., 1997Taylor, 2001Veyradier et al., 2003Noris et al., 2003). Noris and Remuzzi (2009) provided a detailed review of atypical HUS.

Genetic Heterogeneity of Atypical Hemolytic Uremic Syndrome

Atypical HUS is a genetically heterogeneous condition. Susceptibility to the development of the disorder can be conferred by mutations in various components of or regulatory factors in the complement cascade system (Jozsi et al., 2008). See AHUS2 (612922), AHUS3 (612923), AHUS4 (612924), AHUS5 (612925), and AHUS6 (612926). AHUS7 (see 615008) is caused by mutation in the DGKE gene (601440), which is not part of the complement cascade system.