Chronic Granulomatous Disease (CGD)

Summary

Chronic Granulomatous Disease (CGD) is an immunodeficiency caused by a deficiency in the NADPH Oxidase enzyme. This enzyme plays a major role in the respiratory (oxidative) burst of neutrophils, generating reactive oxygen species (ROS) used by neutrophils to kill invading pathogens. As a result of deficient NADPH Oxidase, neutrophils cannot generate these reactive oxygen compounds to effectively kill pathogens. Patients with CGD are particularly susceptible to catalase-positive pathogens which include S. aureus, E. coli, and Aspergillus. The most common form of CGD is inherited in an X-linked recessive pattern. Therefore, most patients with CGD are male. The dihydrorhodamine and nitroblue tetrazolium tests are used to diagnose CGD by assessing the neutrophil oxidative burst.

Key Points

• Chronic Granulomatous Disease
  • Defect in NADPH oxidase
    • Impaired Neutrophil Oxidative Burst and production of reactive oxygen species (e.g. superoxide)
    • Enzyme found in Neutrophil Granules
  • Most common form is X-linked recessive
    • Generally affects male patients
    • Less common mutation is autosomal recessive (low-yield)
  • Immunodeficiency
    • Recurrent infections with catalase-positive organisms
      • e.g. S. aureus, E. coli, Aspergillus
  • Diagnosis assesses respiratory burst in neutrophils
    • Dihydrorhodamine test
      • Hallmark diagnostic test, preferred test in most clinical centers
      • Decreased fluorescent signal on flow cytometry
    • Nitroblue tetrazolium dye reduction test
      • Historical test, not commonly used today
      • Fails to turn blue (no oxidative burst) in CGD