Abstract
Background
Atypical hemolytic uremic syndrome (aHUS) is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Neonatal cases are extremely uncommon. Plasma therapy is the first choice therapy in patients with aHUS based on the belief of an underlying complement dysregulation. Alternatively, eculizumab, which targets complement 5, is used to block complement activation.
Case-diagnosis/treatment
Sudden onset macroscopic hematuria, hypertension, and bruises over the entire body were noted in a 5 day-old newborn. Investigations revealed hemolytic anemia, thrombocytopenia, renal impairment, and a low serum C3, leading to the diagnosis of aHUS. Fresh frozen plasma (FFP) infusions and peritoneal dialysis for acute kidney injury were initiated. This approach yielded full renal and hematological remission. The patient was discharged with FFP infusions, but subsequently developed three life-threatening disease recurrences at 1, 3, and 6 months of age. The last relapse presented with uncontrolled hypertension and impaired renal function while the patient was receiving FFP infusions. After the first dose of eculizumab, his renal and hematological parameters returned to normal and his blood pressure normalized. Genetic screening of the CFH gene revealed a novel homozygous p. Tyr1177Cys mutation.
Conclusion
Eculizumab can be considered as an alternative to plasma therapy in the treatment of specific patients with aHUS, even in infants.
References
Besbas N, Karpman D, Landau D, Loirat C, Proesmans W, Remuzzi G, Rizzoni G, Taylor CM, Van de Kar N, Zimmerhackl LB, European Paediatric Research Group for HUS (2006) A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders. Kidney Int 70:423–431
Scheiring J, Rosales A, Zimmerhackl LB (2010) Clinical practice. Today’s understanding of the haemolytic uraemic syndrome. Eur J Pediatr 169:7–13
Kavanagh D, Goodship T (2010) Genetics and complement in atypical HUS. Pediatr Nephrol 25:2431–2442
Moore I, Strain L, Pappworth I, Kavanagh D, Barlow PN, Herbert AP, Schmidt CQ, Staniforth SJ, Holmes LV, Ward R, Morgan L, Goodship TH, Marchbank KJ (2010) Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. Blood 115:379–387
Delvaeye M, Noris M, De Vriese A, Esmon CT, Esmon NL, Ferrell G, Del-Favero J, Plaisance S, Claes B, Lambrechts D, Zoja C, Remuzzi G, Conway EM (2009) Thrombomodulin mutations in atypical hemolytic-uremic syndrome. N Engl J Med 361:345–357
Menni F, Testa S, Guez S, Chiarelli G, Alberti L, Esposito S (2012) Neonatal atypical hemolytic uremic syndrome due to methylmalonic aciduria and homocystinuria. Pediatr Nephrol 27:1401–1405
Fremeaux-Bacchi V (2012) Treatment of atypical uraemic syndrome in the era of eculizumab. Clin Kidney J 5:4–6
Loirat C, Frèmeaux-Bacchi V (2011) Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 6:60
Waters AM, Licht C (2011) aHUS caused by complement dysregulation: new therapies on the horizon. Pediatr Nephrol 26:41–57
Vaziri-Sani F, Holmberg L, Sjöholm AG, Kristoffersson AC, Manea M, Frémeaux-Bacchi V, Fehrman-Ekholm I, Raafat R, Karpman D (2006) Phenotypic expression of factor H mutations in patients with atypical hemolytic uremic syndrome. Kidney Int 69:981–988
Gruppo RA, Rother RP (2009) Eculizumab for congenital atypical hemolytic uremic syndrome. N Eng J Med 360:544–546
Mache CJ, Acham-Roschitz B, Frèmeaux-Bacchi V, Kirschfink M, Zipfel PF, Roedl S, Vester U, Ring E (2009) Complement inhibitor eculizumab in atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 4:1312–1316
Köse A, Zimmerhackl LB, Jungraithmayr T, Mache C, Nürnberger J (2010) New treatment options for atypical hemolytic uremic syndrome with the complement inhibitor eculizumab. Semin Thromb Hemost 36:669–672
Lapeyraque AL, Frèmeaux-Bacchi V, Robitaille P (2011) Efficacy of eculizumab in patient with factor-H-associated atypical hemolytic uremic syndrome. Pediatr Nephrol 26:621–624
Ariceta G, Arrizabalaga B, Aguirre M, Morteruel E, Lopez-Trascasa M (2012) Eculizumab in the treatment of atypical hemolytic uremic syndrome in infants. Am J Kidney Dis 59:707–710
Acknowledgments
The authors thank Ann-Charlotte Kristoffersson, Department of Pediatrics, Lund University for gene sequencing. This work was supported by The Swedish Research Council (K2010-65X-14008-10-3), The Torsten Söderberg Foundation, Konung Gustaf V:s 80-årsfond, and Crown Princess Lovisa’s Society for Child Care (all to DK). The Nephrogenetics Laboratory was established by the Hacettepe University Infrastructure Project (06A101008). This study was supported by The Scientific Research and Development Office of the Hacettepe University (010A101009).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Besbas, N., Gulhan, B., Karpman, D. et al. Neonatal onset atypical hemolytic uremic syndrome successfully treated with eculizumab. Pediatr Nephrol 28, 155–158 (2013). https://doi.org/10.1007/s00467-012-2296-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-012-2296-4