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

Treatment

• Intravenous immunoglobulin
• Prophylactic antibiotics

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