Pediatric Nephrology

, Volume 22, Issue 11, pp 1967–1970 | Cite as

Ocular involvement in hemolytic uremic syndrome due to factor H deficiency—are there therapeutic consequences?

  • Anis Larakeb
  • Sandrine Leroy
  • Véronique Frémeaux-Bacchi
  • Marta Montchilova
  • Béatrice Pelosse
  • Olivier Dunand
  • Georges Deschênes
  • Albert Bensman
  • Tim UlinskiEmail author
Brief Report


Factor H deficiency is responsible for thrombotic microangiopathy (TMA) via uncontrolled activation of the alternative pathway of the complement system. Ocular TMA has never been reported in patients with factor H abnormalities. A male patient with congenital homozygote factor H deficiency reached end-stage renal disease at the age of 10 years. Hemodialysis was uneventful for 3 years, when, suddenly, unilateral ocular pain and blurred vision occurred while he had febrile pharyngitis. Ophthalmologic examination found vitreous bleeding, elevated ocular pressure, choroidal hemorrhage (ultrasound biomicroscopy) and retinal ischemia (fluorescein angiography). C-reactive protein concentration was increased, while haptoglobin levels remained normal. We suspected that TMA due to factor H deficiency was responsible for the ocular manifestations and immediately initiated daily plasma exchanges (PEs) with fresh frozen plasma (FFP) for 10 days followed by three sessions per week. Factor H serum level increased from 6% to 82%, and C3 level normalized. Progressively, ocular pain decreased, and visual acuity and ophthalmologic findings showed improvement. When there is permanent activation of the alternative pathway in patients with end-stage renal disease (ESRD), the search for secondary targets might be of interest. In nephrectomized patients, no biological parameter can predict isolated ocular TMA. Early ophthalmologic investigation and substitution of factor H via FFP may avoid irreversible damage.


Complement system Factor H Glaucoma Hemolytic uremic syndrome Ocular involvement Plasma exchange Fresh frozen plasma Thrombotic microangiopathy 


  1. 1.
    Pichette V, Querin S, Schurch W, Brun G, Lehner-Netsch G, Delage JM (1994) Familial hemolytic–uremic syndrome and homozygous factor H deficiency. Am J Kidney Dis 24:936–941CrossRefGoogle Scholar
  2. 2.
    Dragon-Durey MA, Fremeaux-Bacchi V, Loirat C, Blouin J, Niaudet P, Deschenes G, Coppo P, Herman Fridman W, Weiss L (2004) Heterozygous and homozygous factor H deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases. J Am Soc Nephrol 15:787–795CrossRefGoogle Scholar
  3. 3.
    Kavanagh D, Kemp EJ, Mayland E, Winney RJ, Duffield JS, Warwick G, Richards A, Ward R, Goodship JA, Goodship TH (2005) Mutations in complement factor I predispose to development of atypical hemolytic uremic syndrome. J Am Soc Nephrol 16:2150–2155CrossRefGoogle Scholar
  4. 4.
    Dragon-Durey MA, Fremeaux-Bacchi V (2005) Atypical haemolytic uraemic syndrome and mutations in complement regulator genes. Springer Semin Immunopathol 27:359–374CrossRefGoogle Scholar
  5. 5.
    te Loo DM, Levtchenko E, Furlan M, Roosendaal GP, van den Heuvel LP (2000) Autosomal recessive inheritance of von Willebrand factor-cleaving protease deficiency. Pediatr Nephrol 14:762–765CrossRefGoogle Scholar
  6. 6.
    Kind T, Levy J, Lee M, Kaicker S, Nicholson JF, Kane SA (2002) Cobalamin C disease presenting as hemolytic–uremic syndrome in the neonatal period. J Pediatr Hematol Oncol 24:327–329CrossRefGoogle Scholar
  7. 7.
    Tsai HM (2006) The molecular biology of thrombotic microangiopathy. Kidney Int 70:16–23CrossRefGoogle Scholar
  8. 8.
    Lambert SR, High KA, Cotlier E, Benz EJ Jr (1985) Serous retinal detachments in thrombotic thrombocytopenic purpura. Arch Ophthalmol 103:1172–1174CrossRefGoogle Scholar
  9. 9.
    Snir M, Cohen S, Ben-Sira I, Buckman G (1985) Retinal manifestations of thrombotic thrombocytopenic purpura (TTP) following use of contraceptive treatment. Ann Ophthalmol 17:109–112PubMedGoogle Scholar
  10. 10.
    Beetari B, Schmidbauer JM, Krevet T, Fischer A, Ruprecht KW (2002) Thrombotic thrombocytopenic purpura (Moschcowitz's disease). Klin Monatsbl Augenheilkd 219:454–457CrossRefGoogle Scholar
  11. 11.
    Feiner M, Odeh M, Oliven A, Friedman Z (2001) Macular infarction in thrombotic thrombocytopenic purpura. Ocul Immunol Inflamm 9:273–275CrossRefGoogle Scholar
  12. 12.
    Nathanson S, Ulinski T, Fremeaux-Bacchi V, Deschenes G (2006) Secondary failure of plasma therapy in factor H deficiency. Pediatr Nephrol 21:1769–1771CrossRefGoogle Scholar
  13. 13.
    McAvoy CE, Silvestri G (2005) Retinal changes associated with type 2 glomerulonephritis. Eye 19:985–989CrossRefGoogle Scholar
  14. 14.
    Licht C, Heinen S, Jozsi M, Loschmann I, Saunders RE, Perkins SJ, Waldherr R, Skerka C, Kirschfink M, Hoppe B, Zipfel PF (2006) Deletion of Lys224 in regulatory domain 4 of factor H reveals a novel pathomechanism for dense deposit disease (MPGN II). Kidney Int 70:42–50CrossRefGoogle Scholar
  15. 15.
    Despriet DD, Klaver CC, Witteman JC, Bergen AA, Kardys I, de Maat MP, Boekhoorn SS, Vingerling JR, Hofman A, Oostra BA, Uitterlinden AG, Stijnen T, van Duijn CM, de Jong PT (2006) Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration. JAMA 296:301–309CrossRefGoogle Scholar
  16. 16.
    Barton CH, Vaziri ND (1979) Central retinal vein occlusion associated with hemodialysis. Am J Med Sci 277:39–47CrossRefGoogle Scholar
  17. 17.
    Siegler RL, Brewer ED, Swartz M (1988) Ocular involvement in hemolytic–uremic syndrome. J Pediatr 112:594–597CrossRefGoogle Scholar
  18. 18.
    Eberhard OK, Labjuhn SO, Olbricht CJ (1995) Ocular involvement in haemolytic uraemic syndrome—case report and review of the literature. Nephrol Dial Transplant 10:266–269PubMedGoogle Scholar
  19. 19.
    Saland JM, Emre SH, Shneider BL, Benchimol C, Ames S, Bromberg JS, Remuzzi G, Strain L, Goodship TH (2006) Favorable long-term outcome after liver–kidney transplant for recurrent hemolytic uremic syndrome associated with a factor H mutation. Am J Transplant 6:1948–1952CrossRefGoogle Scholar

Copyright information

© IPNA 2007

Authors and Affiliations

  • Anis Larakeb
    • 1
  • Sandrine Leroy
    • 1
  • Véronique Frémeaux-Bacchi
    • 2
  • Marta Montchilova
    • 3
  • Béatrice Pelosse
    • 3
  • Olivier Dunand
    • 1
  • Georges Deschênes
    • 4
  • Albert Bensman
    • 1
  • Tim Ulinski
    • 1
    Email author
  1. 1.Department of Pediatric NephrologyHôpital Trousseau, AP-HP & Université Paris VIParisFrance
  2. 2.Hôpital Européen Georges Pompidou, AP-HPParisFrance
  3. 3.Department of Pediatric OphthalmologyHôpital Trousseau, AP-HP & Université Paris VIParisFrance
  4. 4.Department of Pediatric NephrologyHôpital Robert Debré, AP-HP & Université Paris VIIParisFrance

Personalised recommendations