Genetics · MU Sofia

27. Congenital Immunodeficiencies: Phagocyte and Complement Defects

Covers two congenital defects of innate immunity: chronic granulomatous disease, where NADPH oxidase failure stops phagocytes killing certain microbes, and hereditary angioedema, caused by C1 esterase inhibitor deficiency and excess bradykinin. For each, it takes genetics, pathophysiology, clinical features, diagnosis and treatment in turn. It includes a general classification table and a side-by-side comparison table of the two disorders.

Inside: 15 sections · 7 labelled pictures · 4 tables · 14 flashcards · 5 min

Topic 27 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 10 sections, about 499 words (5 min of reading), with 14 flashcards.

In this note

  1. Congenital Immunodeficiencies: Phagocyte and Complement Defects
  2. General Classification
  3. I. PHAGOCYTE DEFECT – CHRONIC GRANULOMATOUS DISEASE (CGD)
  4. Genetic and Molecular Basis
  5. Pathophysiology
  6. Clinical Features
  7. Diagnosis
  8. Treatment
  9. II. COMPLEMENT DEFECT – HEREDITARY ANGIOEDEMA (HAE)
  10. Comparison Table

Congenital Immunodeficiencies: Phagocyte and Complement Defects

Congenital immunodeficiencies involving the phagocytic system or complement cascade lead to recurrent infections and inflammatory dysregulation. These disorders impair the body’s innate defense mechanisms — either by defective intracellular killing of pathogens or loss of complement control, both essential for immune protection and inflammation regulation.

This topic includes:

  • Phagocyte defect: Chronic Granulomatous Disease (CGD)
  • Complement defect: Hereditary Angioedema (HAE)

I. PHAGOCYTE DEFECT – CHRONIC GRANULOMATOUS DISEASE (CGD)

Chronic Granulomatous Disease (CGD) is an inherited phagocyte disorder in which neutrophils and macrophages can ingest but cannot kill certain pathogens, due to defects in the NADPH oxidase complex required for generating reactive oxygen species (ROS). This results in recurrent, severe bacterial and fungal infections and granuloma formation.

Genetic and Molecular Basis

  • Main gene: CYBB on Xp21.1.
  • Other genes (autosomal recessive): NCF1, NCF2 CYBA.
  • Inheritance: X-linked recessive (most common) or autosomal recessive.
  • Defective protein: NADPH oxidase enzyme complex.
  • Molecular consequence: Absent or reduced respiratory burst → no hydrogen peroxide/superoxide production → defective intracellular killing.

Pathophysiology

  1. 1. Phagocytes ingest microbes normally, but fail to destroy them.
  2. 2. Defective NADPH oxidase → no formation of superoxide (O₂⁻) and H₂O₂.
  3. 3. Catalase-positive organisms degrade any available H₂O₂, escaping killing.
  4. 4. Persistent infection triggers macrophage activation → granuloma formation to contain microbes.
  5. 5. Chronic inflammation leads to abscesses and tissue damage in multiple organs.

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