An infant presents at 6 months with severe bacterial infections (Streptococcus pneumoniae sepsis twice) but normal T-cell counts and normal delayed hypersensitivity skin tests. Flow cytometry shows absent B-cells; serum IgG is 120 mg/dL (normal >600). Bone marrow shows arrest at pro-B stage. The most likely molecular defect is in:

• A IL-2 receptor gamma chain (common gamma chain)
• B Adenosine deaminase (ADA)
• C RAG1/RAG2 recombinase
• D Bruton's tyrosine kinase (BTK) ✓

Explanation

X-linked agammaglobulinaemia (Bruton's disease) is caused by a BTK gene mutation on chromosome Xq22. BTK is essential for pre-B-cell receptor signalling; its absence arrests B-cell development at the pro-B to pre-B stage, yielding absent circulating B-cells and near-absent immunoglobulins. T-cells are unaffected. The infant is protected from most infections until maternal IgG wanes at 3–6 months. ADA deficiency and RAG mutations cause SCID with combined B and T-cell deficiency; common gamma chain deficiency also causes SCID.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.