X-linked agammaglobulinemia

Background

• A primary immunodeficiency that causes agammaglobulinemia
• X-linked recessive, so almost all cases are men
  • An autosomal recessive form exists called autosomal recessive agammaglobulinemia
• One of the most common pediatric primary immunodeficiencies, though delayed presentations are possible
  • Average age of diagnosis is 2.5 years, with majority of cases diagnosed by 5 years

Pathophysiology

• Mutation of Bruton's tyrosine kinase (Btk) gene on the X chromosome at Xq21.3-Xq22
• Mutation prevents B cell maturation
• Many, many mutations exist

Clinical Manifestations

• Commonly present with recurrent upper respiratory tract infections, including sinusitis and otitis media
  • Onset of infections is typically around 6 to 9 months after maternal antibodies have dissipated
• Infections may be particularly severe or require admission and intravenous antibiotics
• Recurrent infections with encapsulated bacteria (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae)
• Increased risk of enterovirus infections
• Increased risk of chronic diarrhea (particularly from Giardia duodenalis)

Investigations

• Quantitative immunoglobulins

Management

• Lifelong immunoglobulin replacement