A 4-year-old boy has had recurrent pneumococcal sepsis, meningitis at age 2, and H. influenzae pneumonia. Immunoglobulin levels show IgG 180 mg/dL, IgA undetectable, IgM undetectable. B cells are absent on flow cytometry. T-cell counts are normal. The molecular defect most likely involves:

• A Mutation in BTK (Bruton tyrosine kinase) blocking pro-B to pre-B cell transition ✓
• B Adenosine deaminase deficiency causing toxic accumulation of deoxyadenosine in lymphocyte precursors
• C IL-7 receptor γ-chain (γc) mutation impairing cytokine signaling for lymphocyte development
• D RAG1/RAG2 recombinase deficiency preventing V(D)J recombination

Explanation

X-linked agammaglobulinemia (XLA) results from BTK mutations. BTK is a tyrosine kinase required for signaling downstream of the pre-B cell receptor (pre-BCR); without it, B-cell development arrests at the pro-B to pre-B stage, producing near-absent circulating B cells and all immunoglobulin classes. Boys present after 6 months (maternal IgG wanes) with recurrent infections by encapsulated bacteria. ADA deficiency and γc chain mutations cause SCID with absent T and B cells (and NK cells in γc mutations). RAG deficiency also causes SCID with absent T and B cells.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.