Learning Objective:
Identify primary T-cell immunodeficiencies, their genetic or molecular defects, classic clinical presentations, and key laboratory findings.
Thymic aplasia / 22q11 microdeletion (DiGeorge syndrome, Velocardiofacial syndrome)
Defect
Failure of 3rd and 4th pharyngeal pouch development → absent thymus & parathyroids
Clinical Features
CATCH-22: Cardiac defects (tetralogy, truncus), Abnormal facies, Thymic hypoplasia → T-cell deficiency, Cleft palate, Hypocalcemia → tetany
Key Findings / Lab
↓ T cells, ↓ PTH, ↓ Ca²⁺, absent thymic shadow on CXR
IL-12 receptor deficiency
Defect
↓ Th1 response; autosomal recessive
Clinical Features
Disseminated mycobacterial and fungal infections; may present after BCG vaccination
Key Findings / Lab
↓ IFN-γ, the most common cause of Mendelian susceptibility to mycobacterial disease (MSMD)
Autosomal dominant hyper-IgE syndrome (Job syndrome)
Defect
STAT3 mutation → ↓ Th17 → impaired neutrophil recruitment
Clinical Features
Cold (noninflamed) Staphylococcal abscesses, retained primary teeth, coarse facies, eczema, fractures from minor trauma
Key Findings / Lab
↑ IgE, ↑ eosinophils; ABCDEF mnemonic: Abscesses, Baby teeth, Coarse facies, Dermatologic problems, Elevated IgE, Fractures
Chronic mucocutaneous candidiasis
Defect
T-cell dysfunction, often due to AIRE defects
Clinical Features
Persistent Candida infections of the skin and mucous membranes
Key Findings / Lab
Absent T-cell proliferation to Candida antigens; negative skin test to Candida
Summary table
| Disease | Defect | Clinical Features | Key Findings / Lab |
|---|---|---|---|
| Thymic aplasia / 22q11 microdeletion (DiGeorge syndrome, Velocardiofacial syndrome) | Failure of 3rd and 4th pharyngeal pouch development → absent thymus & parathyroids | CATCH-22: Cardiac defects (tetralogy, truncus), Abnormal facies, Thymic hypoplasia → T-cell deficiency, Cleft palate, Hypocalcemia → tetany | ↓ T cells, ↓ PTH, ↓ Ca²⁺, absent thymic shadow on CXR |
| IL-12 receptor deficiency | ↓ Th1 response; autosomal recessive | Disseminated mycobacterial and fungal infections; may present after BCG vaccination | ↓ IFN-γ, the most common cause of Mendelian susceptibility to mycobacterial disease (MSMD) |
| Autosomal dominant hyper-IgE syndrome (Job syndrome) | STAT3 mutation → ↓ Th17 → impaired neutrophil recruitment | Cold (noninflamed) Staphylococcal abscesses, retained primary teeth, coarse facies, eczema, fractures from minor trauma | ↑ IgE, ↑ eosinophils; ABCDEF mnemonic: Abscesses, Baby teeth, Coarse facies, Dermatologic problems, Elevated IgE, Fractures |
| Chronic mucocutaneous candidiasis | T-cell dysfunction, often due to AIRE defects | Persistent Candida infections of the skin and mucous membranes | Absent T-cell proliferation to Candida antigens; negative skin test to Candida |
High-Yield Mnemonics / Tips
- DiGeorge / CATCH-22: Cardiac, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia
- Job syndrome / ABCDEF: Abscesses, Baby teeth, Coarse facies, Dermatologic problems, Elevated IgE, Fractures
