Bruton Agammaglobulinemia

Bruton Agammaglobulinemia

 

Bruton agammaglobulinemia (X-linked agammaglobulinemia) is a primary immunodeficiency characterized by recurrent bacterial infections in affected males.

Epidemiology

  • Incidence – 1-2 cases per 100,000 male births per year
  • Most commonly diagnosed in whites
  • About 50% of patients are diagnosed by 2 years of age and nearly 80% are diagnosed by school age

Risk Factors

  • Genetics
    • X-linked recessive inheritance
      • Several mutations in the Bruton tyrosine kinase gene have been reported

Pathophysiology

  • Genetic defect leads to deficient development of B lymphocytes and marked reduction in all classes of immunoglobulins
  • Hypogammaglobulinemia results in predisposition to life-threatening infections caused by encapsulated bacteria and enteroviruses

Clinical Presentation

  • Infants are usually asymptomatic during the first 3 months of life due to passive transfer of immunoglobulins by their mothers
  • Most common clinical presentation of disease are infections of upper respiratory airways including:
    • Otitis media
    • Sinusitis
    • Pneumonia
  • Other common infections
    • Conjunctivitis
    • Chronic-recurrent diarrhea
    • Skin infections
  • Life-threatening infections are uncommon
    • Sepsis
    • Meningitis/encephalitis
    • Septic arthritis/osteomyelitis

Diagnosis

  • Laboratory testing
    • Immunoglobulin testing – quantitative
      • IgG typically <200 mg/dL
      • IgM and IgA typically <20 mg/dL
      • Antibody titers to vaccination – typically none found

Differential Diagnosis

  • X-linked hyper IgM syndrome
  • X-linked severe combined immunodeficiencies
  • X-linked neutropenia
  • X-linked lymphoproliferative disease

Treatment

  • Intravenous immunoglobulin
  • Prophylactic antibiotics

See Also