Genetics · MU Sofia

25 –General characteristics and classification of congenital immunodeficiencies. Severe combined immunodeficiency: adenosine deaminase deficiency (ADD). Combined immunodeficiency syndromes: Wiskott-Aldrich syndrome (WAS).

Covers the general features and classification of congenital immunodeficiencies, grouped by affected immune component in a table, then severe combined immunodeficiency with a focus on adenosine deaminase deficiency, including its pathophysiology, clinical features, diagnosis and treatment. It then turns to Wiskott-Aldrich syndrome, outlining its genetic basis, clinical features, diagnostic findings and treatment, and closes with a comparison table of the two disorders.

Inside: 8 sections · 8 labelled pictures · 4 tables · 15 flashcards · 5 min

Topic 25 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 8 sections, about 489 words (5 min of reading), with 15 flashcards.

In this note

  1. 25 –General characteristics and classification of congenital immunodeficiencies. Severe combined immunodeficiency: adenosine deaminase deficiency (ADD). Combined immunodeficiency syndromes: Wiskott-Aldrich syndrome (WAS).
  2. Definition
  3. General Characteristics
  4. Classification of Congenital Immunodeficiencies
  5. I. Severe Combined Immunodeficiency (SCID)
  6. II. Combined Immunodeficiency Syndrome: Wiskott–Aldrich Syndrome (WAS)
  7. Treatment
  8. Key Differences

Definition

Congenital (Primary) Immunodeficiencies are genetically determined defects that impair the development or function of the immune system. They may affect B cells, T cells, phagocytes, complement proteins, or combined pathways, leading to recurrent, severe, or unusual infections, autoimmune phenomena, and sometimes malignancies.

General Characteristics

  • Usually manifest in infancy or early childhood.
  • Patients often present with:
  • Recurrent bacterial, viral, or fungal infections.
  • Poor response to vaccination.
  • Failure to thrive or growth retardation.
  • Most are monogenic disorders, inherited in autosomal recessive or X-linked patterns.
  • Can be classified based on the affected immune component (humoral, cellular, combined, etc.).

I. Severe Combined Immunodeficiency (SCID)

SCID represents a group of severe congenital disorders where both T-cell and B-cell immunity are profoundly impaired. Infants with SCID are extremely vulnerable to infections and typically die early without hematopoietic stem cell transplantation.

Genetic Types and Inheritance

  • X-linked SCID (most common): mutation in IL2RG gene (γ-chain of IL-2 receptor).
  • Autosomal recessive forms:
  • Adenosine deaminase (ADA) deficiency
  • JAK3 deficiency, RAG1/2 mutations, etc.

Adenosine Deaminase (ADA) Deficiency

Pathophysiology:

  1. 1. ADA enzyme is essential in purine metabolism → converts toxic deoxyadenosine to inosine.
  2. 2. ADA deficiency → accumulation of deoxyadenosine and dATP, which are toxic to lymphocytes.
  3. 3. The buildup inhibits DNA synthesis and lymphocyte proliferation.
  4. 4. Leads to severe lymphopenia → both T and B cell function severely compromised.
  5. 5. NK cells are also reduced → combined cellular and humoral immunodeficiency.

Clinical Features

  • Onset in early infancy.
  • Failure to thrive, chronic diarrhea, recurrent severe infections (bacterial, viral, fungal).
  • Oral candidiasis, pneumonia, skin rashes.
  • Absent thymic shadow on chest X-ray (due to thymic hypoplasia).

Diagnosis

  • Lymphopenia (very low T, B, and NK cells).
  • Low serum immunoglobulins.
  • Enzyme assay → absent ADA activity.
  • Confirmed by ADA gene mutation analysis.

Treatment

  • Hematopoietic stem cell transplantation (HSCT): curative in most cases.
  • Enzyme replacement therapy (PEG-ADA): improves survival until transplant.
  • Gene therapy: ADA cDNA introduced into patient’s stem cells – long-term functional correction.

Continue reading free

The whole note, all 8 sections, is free with an AceMed account, with its 15 flashcards. Premium adds flashcard recall, highlights and Ask AI.

Start freeAlready a member? Open the note