Progress in treating chronic granulomatous disease

Br J Haematol. 2021 Jan;192(2):251-264. doi: 10.1111/bjh.16939. Epub 2020 Jul 8.


Chronic granulomatous disease is a primary immunodeficiency due to a defect in one of six subunits that make up the nicotinamide adenine dinucleotide phosphate oxidase complex. The most commonly defective protein, gp91phox , is inherited in an X-linked fashion; other defects have autosomal recessive inheritance. Bacterial and fungal infections are common presentations, although inflammatory complications are increasingly recognized as a significant cause of morbidity and are challenging to treat. Haematopoietic stem cell transplantation offers cure from the disease with improved quality of life; overall survival in the current era is around 85%, with most achieving long-term cure free of medication. More recently, gene therapy is emerging as an alternative approach. Results using gammaretroviral vectors were disappointing with genotoxicity and loss of efficacy, but preliminary results using lentiviral vectors are extremely encouraging.

Keywords: chronic granulomatous disease; gene therapy; haematopoietic stem cell transplantation; infection; inflammation.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Inflammatory Agents / therapeutic use
  • Disease Management
  • Genetic Therapy / methods
  • Granulomatous Disease, Chronic / diagnosis
  • Granulomatous Disease, Chronic / genetics
  • Granulomatous Disease, Chronic / microbiology
  • Granulomatous Disease, Chronic / therapy*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Quality of Life


  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents