A 30-year-old man with a known hereditary immunodeficiency develops recurrent pneumonia with Streptococcus pneumoniae and Haemophilus influenzae (encapsulated bacteria) but NOT recurrent viral or fungal infections. Serum immunoglobulins are markedly reduced (IgG <1 g/L, IgM undetectable, IgA undetectable) but T-cell count is normal. Which genetic defect is the underlying cause?
- A Bruton tyrosine kinase (BTK) mutation causing X-linked agammaglobulinemia ✓
- B RAG1/RAG2 mutation causing failure of V(D)J recombination
- C ADA (adenosine deaminase) deficiency causing SCID
- D CD40L (CD154) mutation causing hyper-IgM syndrome
Explanation
X-linked agammaglobulinemia (Bruton disease) is caused by mutations in BTK (Bruton tyrosine kinase), essential for B-cell maturation beyond the pro-B cell stage. There are virtually no mature B cells, no germinal centers, no tonsils/adenoids, and all immunoglobulin classes are absent. T-cell function is normal (explaining resistance to most viral/fungal infections). Patients develop infections with encapsulated bacteria after maternal IgG wanes (~6 months). Treatment: IVIG. Hyper-IgM syndrome (CD40L/CD40/AID mutations) shows elevated IgM with absent IgG/IgA and susceptibility to Pneumocystis.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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