A 3-year-old boy has recurrent sinopulmonary infections since 6 months of age, absent tonsils, and undetectable immunoglobulins. B cells are absent but T cells and NK cells are normal. Genetic testing shows a BTK mutation. The defective pathway is:

• A T-cell signalling defect impairing T-B cooperation
• B Defective thymic education causing T-cell immunodeficiency
• C Impaired class-switch recombination in mature B cells
• D Pre-BCR to mature B-cell transition blocked at pro-B cell stage ✓

Explanation

X-linked agammaglobulinemia (Bruton's disease) results from BTK (Bruton tyrosine kinase) mutations. BTK is required for pre-BCR signalling that drives pro-B to pre-B cell maturation; without it, B-cell development is arrested at the pro-B cell stage, resulting in absent mature B cells, absent immunoglobulins, and absent tonsils/lymphoid follicles. T cells are normal. Class-switch recombination defects cause Hyper-IgM syndrome; thymic defects cause DiGeorge syndrome.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.