BOF: General (Paediatrics)
- Jun 29, 2016
- 2 min read
Which of the following is NOT a reasonable treatment strategy for chronic granulomatous disease?
a) Allogeneic haematopoietic stem cell transplant from HLA identical sibling donor
b) Corticosteroids
c) Gene therapy using retroviral vectors
d) Interferon gamma
e) White cell (buffy coat) transfusion
Answer:
Gene therapy using retroviral vectors
Explanation:
Chronic granulomatous disease is an immunodeficiency leading to chronic, life threatening infections caused by loss of function or deficiency of any part of the NADPH oxidase enzyme complex. This leads to impaired generation of oxygen radicals and hence persistence of phagocytosed microbes which cannot then be broken down, and susceptibility to severe infections and chronic inflammation.
Most commonly it arises from a mutation in the gene encoding gp91(PHOX) located on chromosome X, but many other loci of mutation have been described. It is usually diagnosed in infancy following recurrent infections, often pneumonia and abscesses, and most commonly involving Staphylococcus, Escherichia coli, Klebsiella spp. and fungal (aspergillus and candida). Functional assay of the neutrophil’s oxidative capacity, either by microscopy (nitroblue tetrazolium dye) or flow cytometry (dihydrorhodamine 123) establishes diagnosis.
The mainstay of treatment is prophylactic and supportive treatment with broad spectrum antibiotics, antifungals and surgery as necessary. The disease may be cured by allogeneic bone marrow transplantation, which is successful in 80% of cases where there is an HLA-matched sibling donor. Interferon gamma has been used as prophylaxis against recurrent infection with some success but is poorly tolerated due to side effects. White cell transfusions may help support through life threatening infections. Crohn’s-like colitis, granulomatous bowel obstruction and miliary pulmonary Aspergillosis may be treated with corticosteroids but these should generally be avoided due to their additional immunosuppressant effect.
Gene therapy has met with some limited success using retroviruses as vectors but with very short duration of efficacy and the concern of oncogenicity. It remains experimental, with limited application as a treatment of last resort for patients without a donor, and within in only a few centres. However there remains optimism that the technique will eventually meet with success and replace allogeneic transplantation.
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