Genetics · MU Sofia

68. Primary immunodeficiencies: SCID, congenital neutropenias, Shwachman-Diamond, agammaglobulinaemia (Bruton), chronic granulomatous disease.

Inside: 40 sections · 22 labelled pictures · 12 tables · 44 flashcards · 15 min

Topic 68 of 79 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 21 sections, about 1,479 words (15 min of reading), with 44 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
  11. Congenital Immunodeficiencies: Humoral and Immune Regulation Defects
  12. General Characteristics
  13. Classification of Congenital Immunodeficiencies
  14. I. Deficiency of Humoral Immunity: X-linked Agammaglobulinemia (XLA)
  15. II. Deficiency of Immune Regulation: Chediak–Higashi Syndrome (CHS)
  16. Definition
  17. Comparison
  18. 25 –General characteristics and classification of congenital immunodeficiencies. Severe combined immunodeficiency: adenosine deaminase deficiency (ADD). Combined immunodeficiency syndromes: Wiskott-Aldrich syndrome (WAS).
  19. I. Severe Combined Immunodeficiency (SCID)
  20. II. Combined Immunodeficiency Syndrome: Wiskott–Aldrich Syndrome (WAS)
  21. Key Differences

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

Continue reading free

The whole note, all 21 sections, is free with an AceMed account, with its 44 flashcards. Premium adds flashcard recall, highlights and Ask AI.

Start freeAlready a member? Open the note