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