USMLE

Chronic Granulomatous Disease (CGD)

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Immunodeficiencies
  1. Selective IgA Deficiency
  2. Chediak-Higashi Syndrome
  3. DiGeorge Syndrome
  4. Bruton (X-linked) Agammaglobulinemia
  5. Hyper-IgM Syndrome
  6. IPEX
  7. Leukocyte Adhesion Deficiency (LAD)
  8. Chronic Granulomatous Disease (CGD)
  9. IL-12 Receptor Deficiency
  10. Wiskott-Aldrich Syndrome

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
    • 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
        • Historical test, not commonly used today
        • Decreased fluorescent signal on flow cytometry
      • Nitroblue tetrazolium dye reduction test
        • Hallmark diagnostic test
        • Fails to turn blue (no oxidative burst) in CGD