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Relative Role of Genetic Complement Abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical Phenotype

Lookup NU author(s): Professor Tim Goodship


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Background and objectives: Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Most childhood cases are caused by Shiga toxin producing bacteria. The other form, atypical HUS (aHUS), accounts for 10% of cases and has a poor prognosis. Genetic complement abnormalities have been found in aHUS. Design, setting, participants, and measurements: We screened 273 consecutive patients with aHUS for complement abnormalities and studied their role in predicting clinical phenotype and response to treatment. We compared mutation frequencies and localization and clinical outcome in familial (82) and sporadic (191) cases. Results: In >70% of sporadic and familial cases, gene mutations, disease-associated factor H (CFH) polymorphisms, or anti-CFH autoantibodies were found. Either mutations or CFH polymorphisms were also found in the majority of patients with secondary aHUS, suggesting a genetic predisposition. Familial cases showed a higher prevalence of mutations in SCR20 of CFH and more severe disease than sporadic cases. Patients with CFH or THBD (thrombomodulin) mutations had the earliest onset and highest mortality. Membrane-cofactor protein (MCP) mutations were associated with the best prognosis. Plasma therapy induced remission in 55 to 80% of episodes in patients with CFH, C3, or THBD mutations or autoantibodies, whereas patients with CFI (factor I) mutations were poor responders. aHUS recurred frequently after kidney transplantation except for patients with MCP mutations. Conclusions: Results underline the need of genetic screening for all susceptibility factors as part of clinical management of aHUS and for identification of patients who could safely benefit from kidney transplant. Clin J Am Soc Nephrol 5: 1844-1859, 2010. doi: 10.2215/CJN.02210310

Publication metadata

Author(s): Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G

Publication type: Article

Publication status: Published

Journal: Clinical Journal of the American Society of Nephrology

Year: 2010

Volume: 5

Issue: 10

Pages: 1844-1859

Print publication date: 01/07/2010

ISSN (print): 1555-9041

ISSN (electronic): 1555-905X

Publisher: American Society of Nephrology


DOI: 10.2215/CJN.02210310


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Funder referenceFunder name
Fondazione ARMR Onlus Aiuti per la Ricerca sulle Malattie Rare (Bergamo, Italy)
Progetto Alice ONLUS (Milan, Italy)
Compagnia di San Paolo (Torino, Italy)
Fondazione ART per la Ricerca sui Trapianti ONLUS (Milan, Italy)
Fondazione Chiesi (Parma, Italy)
Istituto Superiore di Sanita (Rome, Italy)
GGP07193Comitato Telethon Fondazione ONLUS (Roma, Italy)
G0701325UK Medical Research Council