Skip to main content

Advertisement

SpringerLink
Log in

Clinical Manifestations of Disease in X-Linked Carriers of Chronic Granulomatous Disease

  • Key Review Article
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency due to a defect in one of the NADPH oxidase complex subunits; 70 % of cases are X-linked, due to a CYBB mutation, resulting in defective production of gp91PHOX. Female carriers of X-linked CGD have previously been considered to be unaffected. It is increasingly recognized that they may suffer from similar problems to CGD patients. This review will examine the literature about clinical manifestations of disease in X-linked carriers of CGD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Roos D, de Boer M, Kuribayashi F, Meischl C, Weening RS, Segal AW, et al. Mutations in the X-linked and autosomal recessive forms of chronic granulomatous disease. Blood. 1996;87(5):1663–81.

    PubMed  CAS  Google Scholar 

  2. Kuhns D, Alvord WG, Heller TH, 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.

    Article  PubMed  CAS  Google Scholar 

  3. Roesler J, Emmendorffer A. Diagnosis of chronic granulomatous disease. Blood. 1991;78:1387–9.

    PubMed  CAS  Google Scholar 

  4. Jelsness-Jorgensen L-P et al. Chronic fatigue is more prevalent in patients with inflammatory bowel disease than in healthy controls. Inflamm Bowel Dis. 2011;17(7):1564–72.

    Article  PubMed  Google Scholar 

  5. Vowells S, Sekhsaria S, Malech HL, Shalit M, Fleisher TA. Flow cytometric analysis of the granulocyte respiratory burst: a comparison study of fluorescent probes. J Immunol Methods. 1995;178:89–97.

    Article  PubMed  CAS  Google Scholar 

  6. Sillevis Smitt J, Weening RS, Krieg SR, Bos JD. Discoid lupus erythematosus-like lesions in carriers of X-linked chronic granulomatous disease. Br J Dermatol. 1990;122(5):643–50.

    Article  PubMed  CAS  Google Scholar 

  7. Brandrup F, Koch C, Petri M, et al. Discoid lupus erythematosus-like lesions and stomatitis in female carriers of X-linked chronic granulomatous disease. Br J Dermatol. 1981;104:495–505.

    Google Scholar 

  8. Foti C, Cassano N, Martire B, Filotico R, Mastrandrea V, Vena G. Lupus erythematosus-like lesions in a carrier of X-linked chronic graulomatous disease: a case report and personal considerations. Int J Dermatol. 2004;43(11):840–2.

    Article  PubMed  Google Scholar 

  9. Cale CM, Morton L, Goldblatt D. Cutaneous and other lupus-like symptoms in carriers of X-linked chronic granulomatous disease: incidence and autoimmune serology. Clin Exp Immunol. 2007;148:79–84.

    Article  PubMed  CAS  Google Scholar 

  10. Thompson EN. Chronic granulomatous disease - quantitative clinicopathological relationships. Arch Dis Child. 1970;45(239):24.

    Article  PubMed  CAS  Google Scholar 

  11. Garioch J, Sampson JR, Seywright T, Thomson J. Dermatoses in five related female carriers of X-linked chronic granulomatous disease. Br J Dermatol. 1989;121:391–6.

    Article  PubMed  CAS  Google Scholar 

  12. Ortiz-Romero P, Corell-Almuzara A, Lopez-Estebaranz JL, Arranz FR, Ruiz-Contreras J. Lupus like lesions in a patient with X-linked chronic granulomatous disease and recombinant X chromosome. Dermatology. 1997;195(3):280–3.

    Article  PubMed  CAS  Google Scholar 

  13. Humbert J, Fishman CB, Western WL, et al. Frequency of carrier state for X-linked chronic granulomatous disease among females with lupus erythematosus. Clin Genet. 1976;10(1):16–20.

    Article  PubMed  CAS  Google Scholar 

  14. Vanderpump MPJ et al. The incidence of thyroid-disorders in the community- a 20 year follow-up of the Whickham survey. Clin Endocrinol. 1995;43(1):55–68.

    Article  CAS  Google Scholar 

  15. Kragballe K, Borregaard N, Brandrup F, Koch C, et al. Relation of monocyte and neutrophil oxidative metabolism to skin and oral lesions in carriers of chronic granulomatous disease. Clin Exp Immunol. 1981;43:390–8.

    PubMed  CAS  Google Scholar 

  16. Rösen-Wolff A, Soldan W, Heyne K, Bickhardt J, Gahr M, Roesler J. Increased susceptibility of a carrier of X-linked chronic granulomatous disease (CGD) to Aspergillus fumigatus infection associated with age-related skewing of lyonization. Ann Hematol. 2001;80:113–5.

    Article  PubMed  Google Scholar 

  17. Schäppi MG, Smith VV, Goldblatt D, Lindley KJ, Milla PJ. Colitis in chronic granulomatous disease. Arch Dis Child. 2001;84:147–51.

    Article  PubMed  Google Scholar 

  18. Sloan JM, Cameron CHS, Maxwell RJ, McCluskey DR, Collins JSA. Colitis complicating chronic granulomatous disease. A clinicopathological case report. Gut. 1996;38:619–22.

    Article  PubMed  CAS  Google Scholar 

  19. Marciano B, Rosenzweig SD, Holland SM, et al. Gastrointestinal involvement in chronic granulomatous disease. Pediatrics. 2004;114(2):462–8.

    Article  PubMed  Google Scholar 

  20. Moltanyer Y, Geerts WH, Chamberlain DW, Heyworth PG, Noack D, Rae J, et al. Underlying chronic granulomatous disease in a patient with bronchocentric granulomatosis. Thorax. 2003;58:1096–8.

    Article  Google Scholar 

  21. Jaggi P, Scherzer R, Knieper R, Mousa H, Prasad V. Utility of screening for chronic granulomatous disease in patients with inflammatory. Bowel Dis J Clin Immunol. 2011;32(1):78–81.

    Article  Google Scholar 

  22. Worsaae N, Staehr Johansen K, Christensen KC. Impaired in vitro function of neutrophils in Crohns disease. Scand J Gastroenterol. 1982;17(1):91–6.

    Article  PubMed  CAS  Google Scholar 

  23. Emmendörffer A et al. Evaluation of flow cytometric methods for diagnosis of chronic granulomatous disease variants under routine laboratory conditions. Cytometry. 1994;18(3):147–55.

    Article  PubMed  Google Scholar 

  24. Amos E. Immune deficiency and autoimmunity. Autoimmun Rev. 2003;2(6):364–9.

    Article  Google Scholar 

  25. De Ravin S, 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.

    Article  PubMed  Google Scholar 

  26. Yeaman G, Froebel K, Galea G, Ormerod A, Urbaniak SJ. Discoid lupus erythematosus in an X-linked cytochrome-positive carrier of chronic granulomatous disease. Br J Dermatol. 1992;126:60–5.

    Article  PubMed  CAS  Google Scholar 

  27. Cordoba-Guijarro S, Feal C, Dauden E, Fraga J, Garcia-Diez A. Lupus erythematous-like lesions in a carrier of X-linked chronic granulomatous disease. J Eur Acad Dermatol Venereol. 2010;14(5):409–11.

    Article  Google Scholar 

  28. Martin-Villa J, Corell A, Ramos-Amador J, Ruiz-Contreras J, Arnaiz-Villena A. Higher incidence of autoantibodies in X-linked chronic granulomatous disease carriers: random X-chromosome inactivation may be related to autoimmunity. Autoimmunity. 1999;31:261–4.

    Article  PubMed  CAS  Google Scholar 

  29. Wolach B et al. Unusual late presentation of X-linked chronic granulomatous disease in an adult female with a somatic mosaic for a novel mutation in CYBB. Blood. 2005;105(1):61–6.

    Article  PubMed  CAS  Google Scholar 

  30. Martyn L, Lischner HW, Pileggi AJ, Harley RD. Chorioretinal lesions in familial chronic granulomatous disease of childhood. Trans Am Ophthalmol Soc. 1971;69:84–112.

    PubMed  CAS  Google Scholar 

  31. Seong-Joon K, Joong Gon K, Young Suk Y. Chorioretinal lesions in patients with chronic granulomatous disease. Retina. 2003;23(3):360–5.

    Article  Google Scholar 

  32. Valluri S, Chu FC, Smith ME. Ocular pathological findings of chronic granulomatous disease of childhood. Am J Ophthalmol. 1995;120(1):120–3.

    PubMed  CAS  Google Scholar 

  33. Goldblatt D, Butcher J, Thrasher A, Russell-Eggitt I. Chorioretinal lesions in patients and carriers of chronic granulomatous disease. J Pediatr. 1999;134(6):780–3.

    Article  PubMed  CAS  Google Scholar 

  34. Boelaert K, Franklyn JA. Thyroid hormone in health and disease. J Endocrinol. 2005;187(1):1–15.

    Article  PubMed  CAS  Google Scholar 

  35. Lewis E, Singla M, Sergeant S, Koty PP, McPhail LC. X-Linked chronic granulomatous disease secondary to skewed X chromosome inactivation in a female with a novel CYBB mutation and late presentation. Clin Immunol. 2008;129:372–80.

    Article  PubMed  CAS  Google Scholar 

  36. Chollet-Martin S, Lopez A, Gaud C, Henry D, Stos B, El Benna J, et al. Severe X-linked chronic granulomatous disease in two unrelated females. Eur J Pediatr. 2007;166:153–9.

    Article  PubMed  Google Scholar 

  37. Lun A, Roesler J, Renz H. Unusual late onset of X-linked chronic granulomatous disease in an adult woman after unsuspicious childhood. Clin Chem. 2002;48:780–1.

    PubMed  CAS  Google Scholar 

  38. Barton L, Johnson CR. Discoid lupus erythematosus and X-linked chronic granulomatous disease. Pediatr Dermatol. 1986;3(5):376–9.

    Article  PubMed  CAS  Google Scholar 

  39. Moelleri RC, Weinberg AN. Persistent salmonella infection in a female carrier for chronic granulomatous disease. Ann Intern Med. 1970;73(4):595.

    Google Scholar 

  40. Weening RS et al. Clinical differences in chronic granulomatous disease in patients with cytochrome-b-negative or cytochrome-b-positive neutrophils. J Pediatr. 1985;107(1):102–4.

    Article  PubMed  CAS  Google Scholar 

  41. Winkelstein JA et al. Chronic granulomatous disease: report on a national registry of 368 patients. Medicine (Baltimore). 2000;79:155–69.

    Article  CAS  Google Scholar 

  42. Gutierrez MJ et al. Residual NADPH oxidase activity and isolated lung involvement in x-linked chronic granulomatous disease. Case Rep Pediatr. 2012;974561(10):5.

    Google Scholar 

  43. Morte S et al. Production of interleukin-1 by peripheral blood mononuclear cells in patients with chronic fatigue syndrome. J Infect Dis. 1989;159(2):362.

    Article  PubMed  CAS  Google Scholar 

  44. Jendrossek V et al. An in-frame triplet deletion within the gp91-phox gene in an adult X-linked chronic granulomatous disease patient with residual NADPH-oxidase activity. Eur J Haematol. 1997;58(2):78–85.

    Article  PubMed  CAS  Google Scholar 

  45. Foster C, Lehrnbecher T, Mol F, et al. Host defense molecule polymorphisms influence the risk for immune-mediated complications in chronic granulomatous disease. J Clin Invest. 1998;102:2146–55.

    Article  PubMed  CAS  Google Scholar 

  46. Hinz A et al. Fatigue in patients with sarcoidosis, compared with the general population. Gen Hosp Psychiatry. 2011;33(5):462–8.

    Article  PubMed  Google Scholar 

  47. Martinez-Zamora MA, Cervera R, Balasch J. Recurrent miscarriage, antiphospholipid antibodies and the risk of thromboembolic disease. Clin Rev Allergy Immunol. 2012;43(3):265–74.

    Article  PubMed  CAS  Google Scholar 

  48. Roesler J. Carriers of X-linked chronic granulomatouse disease at risk. Clin Immunol. 2009;130:233.

    Article  PubMed  CAS  Google Scholar 

  49. Hafner J, Enderlin A, Seger RA, Wuthrich B, Bruckner-Tudermann, Panizzoni P, et al. Discoid lupus erythematosus-like lesions in carriers of X-linked chronic granulomatous disease. Br J Dermatol. 1992;127:446–7.

    Article  PubMed  CAS  Google Scholar 

  50. Lovas J, Issekutz A, Walsh N, Miller RAW. Lupus erythematosus-like oral mucosal and skin lesions in a carrier of chronic granulomatous disease. Oral Surg Oral Med Oral Pathol. 1995;80(1):78–82.

    Article  CAS  Google Scholar 

  51. Rupec R, Petropoulou TH, Belohradsky BH, et al. Lupus erythematosus tumidus and chronic discoid lupus erythematosus in carriers of X-linked chronic granulomatous disease. Eur J Dermatol. 2000;10(3):184–9.

    PubMed  CAS  Google Scholar 

  52. Johnston RB, Harbeck RJ. Recurrent severe infections in a girl with apparently variable expression of mosaicism for chronic granulomatous disease. J Pediatr. 1985;106(1):50–5.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Cellular Medicine, Newcastle University, London, UK

    A. C. Battersby & A. R. Gennery

  2. Clinical Immunology, Great Ormond Street Hospital, London, UK

    C. M. Cale

  3. Institute of Child Health, University College London, London, UK

    D. Goldblatt

  4. Department Paediatric Immunology & Infectious Diseases, Old Children’s Outpatients, Royal Victoria Infirmary, Newcastle, NE1 4LP, UK

    A. C. Battersby

Authors
  1. A. C. Battersby
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. M. Cale
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Goldblatt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. R. Gennery
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. C. Battersby.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Battersby, A.C., Cale, C.M., Goldblatt, D. et al. Clinical Manifestations of Disease in X-Linked Carriers of Chronic Granulomatous Disease. J Clin Immunol 33, 1276–1284 (2013). https://doi.org/10.1007/s10875-013-9939-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-013-9939-5

Keywords

Search

Navigation