X-linked agammaglobulinemia
USMLE Step 1Difficulty: easyLast updated:
A 14-month-old boy has had recurrent otitis media, two episodes of pneumonia, and sinusitis since 7 months of age; cultures grew Streptococcus pneumoniae and Haemophilus influenzae. A maternal uncle died of infections in childhood. Examination shows very small tonsils and no palpable cervical or inguinal lymph nodes. Serum IgG, IgA, and IgM are all markedly decreased. Flow cytometry shows that fewer than 1% of lymphocytes are CD19+; T-cell numbers are normal.
A mutation in the gene encoding which of the following is the most likely cause?
Answer and explanation
Correct answer: A. Bruton tyrosine kinase
Recurrent pyogenic infections with encapsulated bacteria beginning after maternal antibody wanes, absent tonsils and lymph nodes, panhypogammaglobulinemia, and absent B cells in a boy with an affected maternal uncle indicate X-linked agammaglobulinemia. The source states that the disease results from mutations in an X-chromosome gene encoding Bruton tyrosine kinase (BTK). BTK is essential for B-cell development, and without it maturation stops, so there are no mature B cells and hence no antibodies. As a result, affected boys have very small tonsils and do not develop lymph nodes. Diagnosis is by markedly low IgG, IgA, and IgM with absent B cells (fewer than 1% CD19+ lymphocytes) and genetic testing. Treatment is immune globulin replacement. T-cell numbers and function are preserved.
Each option explained
- A. Bruton tyrosine kinaseCorrect. BTK mutations arrest B-cell maturation, causing absent B cells and agammaglobulinemia.
- B. Adenosine deaminaseIncorrect. Adenosine deaminase deficiency causes SCID with profound T-cell lymphopenia.
- C. Common gamma chain of cytokine receptorsIncorrect. Common gamma chain mutations cause X-linked SCID with absent T cells and NK cells.
- D. WAS proteinIncorrect. WAS mutations cause Wiskott-Aldrich syndrome (eczema, thrombocytopenia with small platelets, infections).
- E. CD40 ligandIncorrect. CD40 ligand deficiency causes X-linked hyper-IgM syndrome; B cells are present and IgM is normal or elevated.
Key point
X-linked agammaglobulinemia (BTK mutation): absent B cells, very low immunoglobulins, and infections with encapsulated bacteria after about 6 months of age.
From the source
“It results from mutations in a gene on the X chromosome that encodes Bruton tyrosine kinase (BTK).”