X-linked agammaglobulinemia is characterized by low levels or absence of Igs and absent B cells, leading to recurrent infections with encapsulated bacteria.

X-linked agammaglobulinemia results from mutations in a gene on the X chromosome that encodes Bruton tyrosine kinase (Btk). Btk is essential for B-cell development and maturation; without it, there are no B cells and hence no antibodies. As a result, male infants have very small tonsils and do not develop lymph nodes; they have recurrent pyogenic lung, sinus, and skin infections with encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae). Patients are also susceptible to persistent CNS infections resulting from live-attenuated oral polio vaccine and from echoviruses and coxsackieviruses; these infections can also manifest as progressive dermatomyositis with or without encephalitis.

With early diagnosis and appropriate treatment, prognosis is good unless CNS viral infections develop.

Diagnosis

• Low Ig levels and absent B cells

Diagnosis is by detecting low IgG levels (< 100 mg/dL) and absent B cells (< 1% CD19+ cells via flow cytometry). Transient neutropenia may also be present. If the mutation has been identified in family members, mutational analysis of chorionic villus, amniocentesis, or percutaneous umbilical cord blood samples can provide prenatal diagnosis.

Treatment

Treatment is IV immune globulin 400 mg/kg once/mo. Prompt use of adequate antibiotics for each infection is crucial; bronchiectasis requires continuous rotation of antibiotics.

Last full review/revision September 2008 by Rebecca H. Buckley, MD