International Journal of Hematology

, Volume 100, Issue 5, pp 437–442 | Cite as

Analysis of patients with atypical hemolytic uremic syndrome treated at the Mie University Hospital: concentration of C3 p.I1157T mutation

  • Takeshi Matsumoto
  • Xinping Fan
  • Eiji Ishikawa
  • Masaaki Ito
  • Keishirou Amano
  • Hidemi Toyoda
  • Yoshihiro Komada
  • Kohshi Ohishi
  • Naoyuki Katayama
  • Yoko Yoshida
  • Masanori Matsumoto
  • Yoshihiro Fujimura
  • Makoto Ikejiri
  • Hideo Wada
  • Toshiyuki Miyata
Original Article

Abstract

Atypical hemolytic uremic syndrome (aHUS) is caused by abnormalities of the complement system and has a significantly poor prognosis. The clinical phenotypes of 12 patients in nine families with aHUS with familial or recurrent onset and ADAMTS13 activity of ≥20 % treated at the Mie University Hospital were examined. In seven of the patients, the first episode of aHUS occurred during childhood and ten patients experienced a relapse. All patients had renal dysfunction and three had been treated with hemodialysis. Seven patients experienced probable triggering events including common cold, influenza, bacterial infection and/or vaccination for influenza. All patients had entered remission, and renal function was improved in 11 patients. DNA sequencing of six candidate genes, identified a C3 p.I1157T missense mutation in all eight patients in six families examined and this mutation was causative for aHUS. A causative mutation THBD p.D486Y was also identified in an aHUS patient. Four missense mutations, CFH p.V837I, p.Y1058H, p.V1060L and THBD p.R403K may predispose to aHUS manifestation; the remaining seven missense mutations were likely neutral. In conclusion, the clinical phenotypes of aHUS are various, and there are often trigger factors. The C3 p.I1157T mutation was identified as the causative mutation for aHUS in all patients examined, and may be geographically concentrated in or around the Mie prefecture in central Japan.

Keywords

aHUS C3 mutation Trigger factor Renal failure Thrombotic microangiopathy 

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Copyright information

© The Japanese Society of Hematology 2014

Authors and Affiliations

  • Takeshi Matsumoto
    • 1
  • Xinping Fan
    • 2
  • Eiji Ishikawa
    • 3
  • Masaaki Ito
    • 3
  • Keishirou Amano
    • 4
  • Hidemi Toyoda
    • 4
  • Yoshihiro Komada
    • 4
  • Kohshi Ohishi
    • 1
  • Naoyuki Katayama
    • 5
  • Yoko Yoshida
    • 6
  • Masanori Matsumoto
    • 6
  • Yoshihiro Fujimura
    • 6
  • Makoto Ikejiri
    • 7
  • Hideo Wada
    • 7
    • 8
  • Toshiyuki Miyata
    • 2
  1. 1.Blood Transfusion ServiceMie University HospitalTsuJapan
  2. 2.Department of Molecular PathogenesisNational Cerebral and Cardiovascular CenterSuitaJapan
  3. 3.Department of Cardiology and NephrologyMie University Graduate School of MedicineTsuJapan
  4. 4.Department of PediatricsMie University Graduate School of MedicineTsuJapan
  5. 5.Department of Hematology and OncologyMie University Graduate School of MedicineTsuJapan
  6. 6.Department of Blood Transfusion MedicineNara Medical UniversityKashiharaJapan
  7. 7.Department of Molecular and Laboratory MedicineMie University Graduate School of MedicineTsuJapan
  8. 8.Department of Laboratory MedicineMie University Graduate School of MedicineTsuJapan

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