A 4-year-old boy with recurrent pneumonias and absent tonsils is found to have undetectable serum immunoglobulins of all classes. A mutation in which gene is the most likely cause of this X-linked condition?

• A BTK (Bruton tyrosine kinase) ✓
• B RAG1 or RAG2 (recombinase activating genes)
• C IL2RG (common gamma chain)
• D ADA (adenosine deaminase)

Explanation

X-linked agammaglobulinemia (Bruton's disease) is caused by loss-of-function mutations in BTK (Bruton tyrosine kinase), located on the X chromosome. BTK is essential for pre-B cell maturation; its absence halts B-cell development at the pre-B stage, resulting in virtual absence of mature B cells, absent lymphoid follicles/tonsils, and undetectable immunoglobulins of all classes. Patients present after 6 months (when maternal IgG wanes) with recurrent bacterial infections. RAG1/2 mutations cause SCID (T and B cell deficiency). IL2RG causes X-linked SCID. ADA deficiency causes autosomal recessive SCID.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.