ORIGINAL ARTICLE Molecular basis and outcomes of atypical haemolytic uraemic syndrome in Czech children Šárka Štolbová 1 & Martin Bezdíčka 1 & Zoltán Prohászka 2 & Dorottya Csuka 2 & Ingrid Hrachovinová 3 & Jan Burkert 4 & Naděžda Šimánková 1 & Štěpánka Průhová 1 & Jakub Zieg 1 Received: 27 October 2019 /Revised: 31 March 2020 /Accepted: 24 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract Atypical haemolytic uraemic syndrome is an ultra-rare, life-threatening disease. Causative variants in genes that encode com- plement factors can be identified in 40–70% of cases. We performed genetic analysis of 21 Czech children with atypical haemolytic uraemic syndrome. Genetic or acquired predisposition to the disease was identified in the majority of our patients: CFHR1 and CFHR3 deletions in 14/21 (67%; 13 of them were positive for anti-complement factor H antibodies), variants in complement genes or DGKE in 13/21 (62%). Multiple genetic findings were identified in eight patients (38%). The incidence of atypical haemolytic uraemic syndrome in the Czech paediatric population was estimated to be 0.092 (CI 0.053–0.131) cases per million inhabitants and 0.92 (CI 0.53–1.32) cases per 100,000 births for the entire reporting period. Ten patients were initially treated with plasma exchange and eight with eculizumab or with a combination of eculizumab and plasma exchange. At the last follow-up, 20 patients were alive and one patient had end-stage renal disease. Conclusion: The incidence of atypical haemolytic uraemic syndrome in the Czech paediatric population corresponds to the reported incidence in Europe. We detected the unusually high rate of CFHR1/CFHR3 deletions associated with anti-complement factor H antibodies in Czech paediatric patients. Treatment by eculizumab led to superior outcomes and prevention of the disease relapses compared with plasma exchange therapy. Our results may help to understand the polygenic nature of atypical haemolytic uraemic syndrome as a disease that results from a combination of various risk factors. What is Known: • Atypical haemolytic uraemic syndrome (aHUS) is considered a polygenic and multifactorial disease. Genetic predisposition to aHUS is identified in 40–70% of children. • Anti-complement factor H antibodies are usually found in 6–25% of affected children. Communicated by Mario Bianchetti Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00431-020-03666-9) contains supplementary material. * Martin Bezdíčka martin.bezdicka@fnmotol.cz Šárka Štolbová sarka.stolbova@fnmotol.cz Zoltán Prohászka prohaszka.zoltan@med.semmelweis-univ.hu Dorottya Csuka csuka.dorottya@med.semmelweis-univ.hu Ingrid Hrachovinová Ingrid.Hrachovinova@uhkt.cz Jan Burkert Jan.Burkert@fnmotol.cz Naděžda Šimánková Nadezda.Simankova@fnmotol.cz Štěpánka Průhová Stepanka.Pruhova@fnmotol.cz Jakub Zieg jakub.zieg@fnmotol.cz Extended author information available on the last page of the article European Journal of Pediatrics https://doi.org/10.1007/s00431-020-03666-9