Journal of Clinical Immunology

, Volume 33, Issue 4, pp 725–730 | Cite as

Diabetes, Renal and Cardiovascular Disease in p47phox−/− Chronic Granulomatous Disease

  • Jennifer W. Leiding
  • Beatriz E. Marciano
  • Christa S. Zerbe
  • Suk See DeRavin
  • Harry L. Malech
  • Steven M. Holland
Original Research


Chronic granulomatous disease is a rare immunodeficiency due to defects in the phagocyte NADPH oxidase. The X-linked form (gp91phox deficiency) accounts for about 70 % of cases; autosomal recessive p47phox deficiency accounts for about 25 % of cases. We identified a 10 % incidence of diabetes in p47phox deficient CGD, but none in X-linked CGD. Renal and cardiovascular diseases were also higher in p47phox deficiency. p47phox deficient CGD has non-infectious morbidities distinct from those in X-linked CGD.


Chronic granulomatous disease p47phox diabetes kidney renal 


  1. 1.
    Holland SM. Chronic granulomatous disease. Clin Rev Allergy Immunol. 2010;38(1):3–10.PubMedCrossRefGoogle Scholar
  2. 2.
    Matute JD, Arias AA, Wright NA, Wrobel I, Waterhouse CC, Li XJ, et al. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Blood. 2009;114(15):3309–15. Epub 2009/08/21.PubMedCrossRefGoogle Scholar
  3. 3.
    Ushio-Fukai M. Localizing NADPH oxidase-derived ROS. Sci STKE. 2006;2006(349):re8. Epub 2006/08/24.PubMedGoogle Scholar
  4. 4.
    Martire B, Rondelli R, Soresina A, Pignata C, Broccoletti T, Finocchi A, et al. Clinical features, long-term follow-up and outcome of a large cohort of patients with Chronic Granulomatous Disease: an Italian multicenter study. Clin Immunol. 2008;126(2):155–64. Epub 2007/11/27.PubMedCrossRefGoogle Scholar
  5. 5.
    Winkelstein JA, Marino MC, Johnston Jr RB, Boyle J, Curnutte J, Gallin JI, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000;79(3):155–69. Epub 2000/06/09.Google Scholar
  6. 6.
    Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Marciano BE, et al. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010;363(27):2600–10. Epub 2010/12/31.PubMedCrossRefGoogle Scholar
  7. 7.
    Wynne SM, Kwon-Chung KJ, Shea YR, Filie AC, Varma A, Lupo P, et al. Invasive infection with Trichosporon inkin in 2 siblings with chronic granulomatous disease. J Allergy Clin Immunol. 2004;114(6):1418–24. Epub 2004/12/04.PubMedCrossRefGoogle Scholar
  8. 8.
    Nerurkar LS, Jacob A, Zeligs B, Walser J, Yeager Jr H, Bellanti JA. Chronic granulomatous disease in an adult. South Med J. 1987;80(10):1296–302. Epub 1987/10/01.PubMedCrossRefGoogle Scholar
  9. 9.
    Siddiqui S, Anderson VL, Hilligoss DM, Abinun M, Kuijpers TW, Masur H, et al. Fulminant mulch pneumonitis: an emergency presentation of chronic granulomatous disease. Clin Infect Dis. 2007;45(6):673–81. Epub 2007/08/23.PubMedCrossRefGoogle Scholar
  10. 10.
    Bolanowski A, Mannon RB, Holland SM, Malech HL, Aschan J, Palmblad J, et al. Successful renal transplantation in patients with chronic granulomatous disease. Am J Transplant. 2006;6(3):636–9. Epub 2006/02/14.PubMedCrossRefGoogle Scholar
  11. 11.
    Walther MM, Malech H, Berman A, Choyke P, Venzon DJ, Linehan WM, et al. The urological manifestations of chronic granulomatous disease. J Urol. 1992;147(5):1314–8. Epub 1992/05/01.PubMedGoogle Scholar
  12. 12.
    Carson MJ, Chadwick DL, Brubaker CA, Cleland RS, Landing BH. Thirteen boys with progressive septic granulomatosis. Pediatrics. 1965;35:405–12. Epub 1965/03/01.PubMedGoogle Scholar
  13. 13.
    Dilworth JA, Mandell GL. Adults with chronic granulomatous disease of “childhood”. Am J Med. 1977;63(2):233–43. Epub 1977/08/01.PubMedCrossRefGoogle Scholar
  14. 14.
    Kimpen J, Van Damme-Lombaerts R, Van den Berghe G, Proesmans W. Autosomal recessive chronic granulomatous disease associated with 18q-syndrome and end-stage renal failure due to Henoch-Schonlein nephritis. Eur J Pediatr. 1991;150(5):325–6. Epub 1991/03/01.PubMedCrossRefGoogle Scholar
  15. 15.
    van Rhenen DJ, Koolen MI, Feltkamp-Vroom TM, Weening RS. Immune complex glomerulonephritis in chronic granulomatous disease. Case report of an eighteen-year-old girl. Acta Med Scand. 1979;206(3):233–7. Epub 1979/01/01.PubMedGoogle Scholar
  16. 16.
    Frifelt JJ, Schonheyder H, Valerius NH, Strate M, Starklint H. Chronic granulomatous disease associated with chronic glomerulonephritis. Acta Paediatr Scand. 1985;74(1):152–7. Epub 1985/01/01.PubMedCrossRefGoogle Scholar
  17. 17.
    Forbes GS, Hartman GW, Burke EC, Segura JW. Genitourinary involvement in chronic granulomatous disease of childhood. AJR Am J Roentgenol. 1976;127(4):683–6. Epub 1976/10/01.PubMedCrossRefGoogle Scholar
  18. 18.
    De Seigneux R, Kanfer A, Terrioux P, Sraer JD, Whitworth JA. Letter: Renal amyloidosis in chronic granulomatous disease. Br Med J. 1974;4(5938):230. Epub 1974/10/26.PubMedCrossRefGoogle Scholar
  19. 19.
    Dechelette E, Rossignol AM, Gout JP, Poirot P, Frappat P, Bost M. [Renal amylosis and chronic septic granulomatosis. Apropos of a case]. Pediatrie. 1977;32(6):UNKNOWN. Epub 1977/09/01. Amylose renale et granulomatose septique chronique. A propos d’une observation.Google Scholar
  20. 20.
    Kaltenis P, Mudeniene V, Maknavicius S, Seinin D. Renal amyloidosis in a child with chronic granulomatous disease and invasive aspergillosis. Pediatr Nephrol. 2008;23(5):831–4. Epub 2008/01/12.PubMedCrossRefGoogle Scholar
  21. 21.
    Peces R, Ablanedo P, Seco M. [Amyloidosis associated with chronic granulomatous disease in a patient with a renal transplant and recurrent urinary tract infections]. Nefrologia. 2002;22(5):486–91. Epub 2002/12/25. Amiloidosis asociada a enfermedad granulomatosa cronica en una paciente con un trasplante renal e infecciones urinarias de repeticion.PubMedGoogle Scholar
  22. 22.
    Yamazaki H, Nishi S, Chou T, Nakagawa Y, Shimada H, Nunoi H, et al. Two brothers with p47-phox-deficient chronic granulomatous disease associated with end-stage renal failure. Nephrol Dial Transplant. 1995;10(12):2334–6. Epub 1995/12/01.PubMedGoogle Scholar
  23. 23.
    Hafner J, Enderlin A, Seger RA, Wuthrich B, Bruckner-Tudermann L, Panizzoni P, et al. Discoid lupus erythematosus-like lesions in carriers of X-linked chronic granulomatous disease. Br J Dermatol. 1992;127(4):446–7. Epub 1992/10/01.PubMedCrossRefGoogle Scholar
  24. 24.
    De Ravin SS, Naumann N, Cowen EW, Friend J, Hilligoss D, Marquesen M, et al. Chronic granulomatous disease as a risk factor for autoimmune disease. J Allergy Clin Immunol. 2008;122(6):1097–103.PubMedCrossRefGoogle Scholar
  25. 25.
    Tse HM, Thayer TC, Steele C, Cuda CM, Morel L, Piganelli JD, et al. NADPH oxidase deficiency regulates Th lineage commitment and modulates autoimmunity. J Immunol. 2010;185(9):5247–58. Epub 2010/10/01.PubMedCrossRefGoogle Scholar
  26. 26.
    Roos D, Kuhns DB, Maddalena A, Bustamante J, Kannengiesser C, de Boer M, et al. Hematologically important mutations: the autosomal recessive forms of chronic granulomatous disease (second update). Blood Cells Mol Dis. 2010;44(4):291–9. Epub 2010/02/20.PubMedCrossRefGoogle Scholar
  27. 27.
    Gorlach A, Lee PL, Roesler J, Hopkins PJ, Christensen B, Green ED, et al. A p47-phox pseudogene carries the most common mutation causing p47-phox- deficient chronic granulomatous disease. J Clin Invest. 1997;100(8):1907–18. Epub 1997/10/23.PubMedCrossRefGoogle Scholar
  28. 28.
    Brunson T, Wang Q, Chambers I, Song Q. A copy number variation in human NCF1 and its pseudogenes. BMC Genet. 2010;11:13. Epub 2010/02/25.PubMedCrossRefGoogle Scholar
  29. 29.
    Pignatelli P, Carnevale R, Di Santo S, Bartimoccia S, Sanguigni V, Lenti L, et al. Inherited human gp91phox deficiency is associated with impaired isoprostane formation and platelet dysfunction. Arterioscler Thromb Vasc Biol. 2011;31(2):423–34. Epub 2010/11/13.PubMedCrossRefGoogle Scholar
  30. 30.
    Violi F, Sanguigni V, Carnevale R, Plebani A, Rossi P, Finocchi A, et al. Hereditary deficiency of gp91(phox) is associated with enhanced arterial dilatation: results of a multicenter study. Circulation. 2009;120(16):1616–22. Epub 2009/10/07.PubMedCrossRefGoogle Scholar
  31. 31.
    Loukogeorgakis SP, van den Berg MJ, Sofat R, Nitsch D, Charakida M, Haiyee B, et al. Role of NADPH oxidase in endothelial ischemia/reperfusion injury in humans. Circulation. 2010;121(21):2310–6. Epub 2010/05/19.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York (outside the USA) 2013

Authors and Affiliations

  • Jennifer W. Leiding
    • 1
    • 3
  • Beatriz E. Marciano
    • 1
  • Christa S. Zerbe
    • 1
  • Suk See DeRavin
    • 2
  • Harry L. Malech
    • 2
  • Steven M. Holland
    • 1
  1. 1.Laboratories of Clinical Infectious DiseasesNational Institutes of HealthBethesdaUSA
  2. 2.Host Defenses, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaUSA
  3. 3.Department of Pediatrics, Division of Allergy, Immunology, and RheumatologyUniversity of South FloridaSt. PetersburgUSA

Personalised recommendations