Neonatal onset atypical hemolytic uremic syndrome successfully treated with eculizumab
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.
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.
Eculizumab can be considered as an alternative to plasma therapy in the treatment of specific patients with aHUS, even in infants.
KeywordsAtypical hemolytic uremic syndrome Complement factor H mutation Eculizumab Newborn
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).
- 1.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 70:423–431PubMedGoogle Scholar
- 4.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 115:379–387PubMedCrossRefGoogle Scholar