Skip to main content

Advertisement

SpringerLink
Log in

Chronic Granulomatous Disease: Two Decades of Experience From a Tertiary Care Centre in North West India

  • Original Research
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Chronic granulomatous disease (CGD) results from an inherited defect in the phagocytic cells of the immune system. It is a genetically heterogenous disease caused by defects in one of the five major subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. There is a paucity of data from India on CGD. We herein describe the clinical features in 17 children with CGD from a single tertiary referral center in India. A detailed analysis of the clinical features, laboratory investigations and outcome of 17 children 7 with X-linked (XL) and 10 with autosomal recessive (AR) form was performed. Diagnosis of CGD was based on an abnormal granulocyte oxidative burst evaluated by either Nitroblue Tetrazolium (NBT) test or flow cytometry based Dihyrorhodamine 123 assay or both. The molecular diagnosis was confirmed by genetic mutation analysis in 13 cases. The mean age at diagnosis and the age at onset of symptoms was significantly lower in children diagnosed with XL- CGD compared those with AR disease. Mutations were detected in CYBB gene in 6 patients with XL-CGD and NCF-1 gene mutations were observed in 7 cases of AR- CGD. The course and outcome of the disease was much worse in children diagnosed with X-linked form of disease compared to AR forms of the disease; 4/7 (57 %) children with X-CGD were dead at the time of data analysis. This is one of the largest series on chronic granulomatous disease from any developing country.

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
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. 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.

    Article  CAS  Google Scholar 

  2. Janeway CACJ, Davidson M, Downey W, Gitlin D, Sullivan JC. Hypergammaglobulinemia associated with severe, recurrent, and chronic non-specific infection. Am J Dis Child. 1954;88:388–92.

    Google Scholar 

  3. Berendes H, Bridges RA, Good RA. A fatal granulomatosus of childhood: the clinical study of a new syndrome. Minn Med. 1957;40(5):309–12.

    CAS  PubMed  Google Scholar 

  4. Bridges RA, Berendes H, Good RA. A fatal granulomatous disease of childhood; the clinical, pathological, and laboratory features of a new syndrome. Am J Dis Child. 1959;97(4):387–408.

    Article  CAS  Google Scholar 

  5. Kuijpers T, Lutter R. Inflammation and repeated infections in CGD: two sides of a coin. Cell Mol Life Sci. Jan;69(1):7–15.

  6. Ushio-Fukai M. Localizing NADPH oxidase-derived ROS. Sci STKE. 2006;2006(349):re8.

    PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. Park BH, Holmes BM, Rodey GE, Good RA. Nitroblue-tetrazolium test in children with fatal granulomatous disease and newborn infants. Lancet. 1969;1(7586):157.

    Article  CAS  PubMed  Google Scholar 

  9. Baehner RL, Nathan DG. Quantitative nitroblue tetrazolium test in chronic granulomatous disease. N Engl J Med. 1968;278(18):971–6.

    Article  CAS  PubMed  Google Scholar 

  10. Emmendorffer A, Hecht M, Lohmann-Matthes ML, Roesler J. A fast and easy method to determine the production of reactive oxygen intermediates by human and murine phagocytes using dihydrorhodamine 123. J Immunol Methods. 1990;131(2):269–75.

    Article  CAS  PubMed  Google Scholar 

  11. Roesler J, Hecht M, Freihorst J, Lohmann-Matthes ML, Emmendorffer A. Diagnosis of chronic granulomatous disease and of its mode of inheritance by dihydrorhodamine 123 and flow microcytofluorometry. Eur J Pediatr. 1991;150(3):161–5.

    Article  CAS  PubMed  Google Scholar 

  12. Salaria M, Singh S, Kumar L, Datta U, Sehgal S. Chronic granulomatous disease. Indian Pediatr. 1999;36(6):594–6.

    CAS  PubMed  Google Scholar 

  13. Nair PS, Moorthy PK, Suprakasan S, Jayapalan S, Preethi K. Chronic granulomatous disease. Indian J Dermatol Venereol Leprol. 2005;71(3):199–201.

    Article  PubMed  Google Scholar 

  14. Pinto LM, Udwadia ZF. A 24-year-old man with giddiness, hemoptysis, and skin lesions. Chest. 2008;134(5):1084–7.

    Article  PubMed  Google Scholar 

  15. Soneja M, Batra A, Vikram NK, Ahuja A, Mohan A, Sood R. Actinomycosis and nocardiosis co-infection in chronic granulomatous disease. J Assoc Physicians India. Apr;60:66–8.

  16. Verma S, Sharma PK, Sivanandan S, Rana N, Saini S, Lodha R, et al. Spectrum of primary immune deficiency at a tertiary care hospital. Indian J Pediatr. 2008;75(2):143–8.

    Article  PubMed  Google Scholar 

  17. Ahlin A, De Boer M, Roos D, Leusen J, Smith CI, Sundin U, et al. Prevalence, genetics and clinical presentation of chronic granulomatous disease in Sweden. Acta Paediatr. 1995;84(12):1386–94.

    Article  CAS  PubMed  Google Scholar 

  18. Liese J, Kloos S, Jendrossek V, Petropoulou T, Wintergerst U, Notheis G, et al. Long-term follow-up and outcome of 39 patients with chronic granulomatous disease. J Pediatr. 2000;137(5):687–93.

    Article  CAS  PubMed  Google Scholar 

  19. Koker MY, Camcioglu Y, van Leeuwen K, Kilic SS, Barlan I, Yilmaz M, et al. Clinical, functional, and genetic characterization of chronic granulomatous disease in 89 Turkish patients. J Allergy Clin Immunol. Jul 30.

  20. El Kares R, Barbouche MR, Elloumi-Zghal H, Bejaoui M, Chemli J, Mellouli F, et al. Genetic and mutational heterogeneity of autosomal recessive chronic granulomatous disease in Tunisia. J Hum Genet. 2006;51(10):887–95.

    Article  PubMed  Google Scholar 

  21. Reich D, Thangaraj K, Patterson N, Price AL, Singh L. Reconstructing Indian population history. Nature. 2009;461(7263):489–94.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. van den Berg JM, van Koppen E, Ahlin A, Belohradsky BH, Bernatowska E, Corbeel L, et al. Chronic granulomatous disease: the European experience. PLoS One. 2009;4(4):e5234.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Finn A, Hadzic N, Morgan G, Strobel S, Levinsky RJ. Prognosis of chronic granulomatous disease. Arch Dis Child. 1990;65(9):942–5.

    Article  CAS  PubMed  Google Scholar 

  25. van Montfrans JM, Rudd E, van de Corput L, Henter JI, Nikkels P, Wulffraat N, et al. Fatal hemophagocytic lymphohistiocytosis in X-linked chronic granulomatous disease associated with a perforin gene variant. Pediatr Blood Cancer. 2009;52(4):527–9.

    Article  PubMed  Google Scholar 

  26. Parekh C, Hofstra T, Church JA, Coates TD. Hemophagocytic lymphohistiocytosis in children with chronic granulomatous disease. Pediatr Blood Cancer. Mar;56(3):460–2.

  27. Alvarez-Cardona A, Rodriguez-Lozano AL, Blancas-Galicia L, Rivas-Larrauri FE, Yamazaki-Nakashimada MA. Intravenous immunoglobulin treatment for macrophage activation syndrome complicating chronic granulomatous disease. J Clin Immunol. Apr;32(2):207–11.

  28. Lee PP, Chan KW, Jiang L, Chen T, Li C, Lee TL, et al. Susceptibility to mycobacterial infections in children with X-linked chronic granulomatous disease: a review of 17 patients living in a region endemic for tuberculosis. Pediatr Infect Dis J. 2008;27(3):224–30.

    Article  PubMed  Google Scholar 

  29. Bustamante J, Aksu G, Vogt G, de Beaucoudrey L, Genel F, Chapgier A, et al. BCG-osis and tuberculosis in a child with chronic granulomatous disease. J Allergy Clin Immunol. 2007;120(1):32–8.

    Article  PubMed  Google Scholar 

  30. Bustamante J, Arias AA, Vogt G, Picard C, Galicia LB, Prando C, et al. Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease. Nat Immunol. Mar;12(3):213–21.

  31. Hasui M. Chronic granulomatous disease in Japan: incidence and natural history. The Study Group of Phagocyte Disorders of Japan. Pediatr Int. 1999;41(5):589–93.

    Article  CAS  PubMed  Google Scholar 

  32. Mouy R, Fischer A, Vilmer E, Seger R, Griscelli C. Incidence, severity, and prevention of infections in chronic granulomatous disease. J Pediatr. 1989;114(4 Pt 1):555–60.

    Article  CAS  PubMed  Google Scholar 

  33. Roos D, Kuhns DB, Maddalena A, Roesler J, Lopez JA, Ariga T, et al. Hematologically important mutations: X-linked chronic granulomatous disease (third update). Blood Cells Mol Dis. Oct 15;45(3):246–65.

  34. 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. Apr 15;44(4):291–9.

  35. Casimir CM, Bu-Ghanim HN, Rodaway AR, Bentley DL, Rowe P, Segal AW. Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat. Proc Natl Acad Sci U S A. 1991;88(7):2753–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. 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. Dec 30;363(27):2600–10.

Download references

Author information

Authors and Affiliations

  1. Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Amit Rawat, Surjit Singh, Deepti Suri & Anju Gupta

  2. Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Biman Saikia, Ranjana Walker Minz & Shobha Sehgal

  3. Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Kim Vaiphei

  4. Department of Pediatrics, National Defense Medical College, Tokorozawa, Saitama, Japan

    C. Kamae, K. Honma, N. Nakagawa, K. Imai & S. Nonoyama

  5. Kazusa DNA Research Institute, Kisarazu, Chiba, Japan

    K. Oshima, N. Mitsuiki & O. Ohara

  6. Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region, China

    Koon-Wing Chan & Yu Lung Lau

Authors
  1. Amit Rawat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Surjit Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Deepti Suri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anju Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Biman Saikia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ranjana Walker Minz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shobha Sehgal
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kim Vaiphei
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C. Kamae
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K. Honma
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. N. Nakagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. K. Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. S. Nonoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. K. Oshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. N. Mitsuiki
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. O. Ohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Koon-Wing Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Yu Lung Lau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Surjit Singh.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(JPEG 8 kb)

High resolution image (TIFF 202 kb)

ESM 2

(JPEG 8 kb)

High resolution image (TIFF 246 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rawat, A., Singh, S., Suri, D. et al. Chronic Granulomatous Disease: Two Decades of Experience From a Tertiary Care Centre in North West India. J Clin Immunol 34, 58–67 (2014). https://doi.org/10.1007/s10875-013-9963-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-013-9963-5

Keywords

Search

Navigation