• Definition: X-linked recessive disease that causes a complete deficiency of mature B lymphocytes
• Epidemiology: occurs mainly in boys
• Etiology: defect of Bruton tyrosine kinase (BTK) expressed in B cells → complete deficiency of mature B cells
• Clinical features: Symptoms develop between 3 and 6 months of age when maternal IgG levels in fetal serum start to decrease.
  • Hypoplasia of lymphoid tissue (e.g., tonsils, lymph nodes)
  • Recurrent, severe, pyogenic infections (e.g., pneumonia, otitis media), especially with encapsulated bacteria (S. pneumoniae, N. meningitidis, and H. influenzae)
  • Hepatitis virus and enterovirus (e.g., Coxsackie virus) infections
• Diagnosis
  • Flow cytometry
    • Absent or low levels of B cells (marked by CD19, CD20, and CD21)
    • Normal or high T cells
  • Low immunoglobulins of all classes
  • Absent lymphoid tissue, i.e., no germinal centers and primary follicles

XLA vs CVID

• XLA presents early (infancy) due to a complete failure in B-cell development from birth.
• CVID presents later (pubertal or post-pubertal) because it involves a gradual decline in B-cell function, leading to a delayed onset of immune deficiency symptoms.