Chronic Granulomatous Disease



Chronic granulomatous disease (CGD) is a rare, primary immunodeficiency caused by a genetic defect that results in an inability of phagocytes to generate superoxide, which is important in microbial killing. Affected individuals are susceptible to recurrent, life-threatening bacterial and fungal infections.



1:200,000 to 1:250,000 live births in the United States and Europe. Rates in other countries vary depending on ethnic practices and degree of intermarriage.

Risk Factors


  • Mutations in any of the five genes that code for the five subunits of the phagocyte NADPH oxidase complex (phox) can result in CGD.
  • Mutations in the gp91phox subunit (CYBB) are responsible for 65% of cases and are inherited in an X-linked manner (1/3 of these cases are the result of a de novo mutation).
  • Mutations in p47phox, p22phox, p67phox, and p40phox subunits account for the remaining cases and have an autosomal recessive inheritance.
  • Mutations in the p47phox subunit are the most common cause of autosomal recessive CGD (25% of all cases).


  • Phagocytes (neutrophils, monocytes, and macrophages) require NADPH oxidase to generate reactive oxygen species (ROS) in a process called the respiratory burst.
  • During this process, the NADPH oxidase complex transfers an electron to molecular oxygen forming superoxide, which is eventually converted to hydrogen peroxide.
  • Superoxide plays a significant role in killing bacterial and fungal pathogens both directly and through the activation of more important intraphagosomal proteases.
  • The clinical phenotype of CGD is related to the level of residual superoxide production; patients who have higher levels of superoxide production have better long-term survival rates.
  • Only the X-linked subunit gp91phox is phagocyte specific, and patients with defects in the autosomal subunits may also have other abnormalities such as vascular disease, diabetes, and inflammatory bowel disease.


CGD is the result of a spontaneous or inherited genetic mutation that is present at birth.

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