Bruton Agammaglobulinemia

Snapshot

• A 6-year-old boy presents to the hospital with a severe upper respiratory infection requiring  hospitalization. Chart review reveals that he has presented multiple times to the emergency room and primary care physician’s office for a variety of infections, including otitis media, upper respiratory infections, pneumonia, and sinusitis. When detailing family history, it is found that his maternal uncle died of an infection as a child. Lab findings include decreased levels of IgG, IgM, and IgA.

Introduction

• Primary humoral immunodeficiency characterized by decreased immunoglobulins
• Genetics
  • X-linked recessive  
    • seen in male children
• Pathogenesis
  • defect in Bruton tyrosine kinase (BTK)   
  • defective maturation of B-cells 
    • impaired signaling from pre-B-cell receptor 
    • ↓ B-cells 
    • ↓ production of all classes of Ig 
• impaired antibody immune response

Presentation

• Symptoms
  • recurrent infections
    • especially after 6 months old (↓ maternal IgG) 
    • Streptococcus pneumoniae, Hemophilus influenzae, Streptoccocus pyogenes, and Pseudomonas
  • increased susceptibility to encapsulated bacteria and blood-borne viruses
    • due to opsonization defect
• Physical exam
• absent/scant lymphoid tissues (tonsils/lymph nodes)

Evaluation

• Diagnosis based on family history, clinical history, and exam
• Serologies
  • ↓ all classes of Ig
  • ↓ levels of B-cells
  • normal T-cells
• Diagnosis confirmed with DNA, mRNA, or protein analysis showing mutation in BTK

Differential Diagnosis

• Common variable immunodeficiency 
• Severe combined immunodeficiency 
• Transient hypogammaglobulinemia of infancy 

Treatment

• Antibiotics for infections
• Regular IVIG infusions

Prognosis, Prevention, and Complications

• Prognosis
  • normal prognosis with regular IVIG therapy and early detection
• Prevention
  • screening in newborns
  • regular IVIG to prevent infections
• Complications
• small risk of malignancy