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Semin Thromb Hemost 2014; 40(04): 422-430
DOI: 10.1055/s-0034-1375296
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Genetics of Atypical Hemolytic Uremic Syndrome (aHUS)

Santiago Rodríguez de Córdoba
1   Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas and Centro de Investigación Biomédica en Enfermedades Raras, Madrid, Spain
,
Marta Subías Hidalgo
1   Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas and Centro de Investigación Biomédica en Enfermedades Raras, Madrid, Spain
,
Sheila Pinto
1   Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas and Centro de Investigación Biomédica en Enfermedades Raras, Madrid, Spain
,
Agustín Tortajada
1   Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas and Centro de Investigación Biomédica en Enfermedades Raras, Madrid, Spain
› Author Affiliations
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Publication History

Publication Date:
05 May 2014 (online)

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Abstract

Hemolytic uremic syndrome (HUS) is a rare, life-threatening disease characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. The atypical form of HUS (aHUS), representing 5 to 10% of cases, lacks the association with infection by Shiga toxin producing Escherichia coli strains that characterizes the commonest clinical presentation of HUS. In the majority of aHUS cases, the disease results from the complement-mediated damage to the microvascular endothelium because of inherited defects in complement genes or autoantibodies against complement regulatory proteins. Incomplete penetrance of aHUS in carriers of mutations is common to all aHUS-associated complement genes and it is now established that the overall genetic predisposition to aHUS of an individual results from the combination of different inherited factors. Moreover, the patient's genotype influences the clinical evolution, the response to plasma therapies, and the recurrence after transplantation. Here, we describe the genetic component of aHUS, the lessons that we have learned from the functional characterization of the aHUS-associated mutations, and the benefits of a comprehensive genetic analysis of the patients.

Keywords

complement - aHUS - thrombotic microangiopathy
 

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