Snapshot A 3-year-old boy is brought to the pediatrician’s office for an ear infection. He has had multiple upper respiratory, ear, and skin infections since 6 months of age. He has required inpatient admissions to the pediatric ward twice for intravenous antibiotics. On physical exam, he has no tonsils and has no history of tonsillectomy. Levels of IgG, IgM, and IgA are decreased. Genetic testing is sent to confirm the diagnosis. Introduction Clinical definition primary humoral immunodeficiency characterized by decreased immunoglobulins Epidemiology Demographics boys etiology Pathogenesis defective maturation of B-cells impaired signaling from pre-B cell receptor ↓ B-cells ↓ production of all classes of Ig impaired antibody immune response Genetics X-linked recessive defect in Bruton tyrosine kinase (BTK) Presentation Symptoms recurrent infections after 6 months of age due to decreased maternal IgG Streptococcus pneumoniae, Hemophilus influenzae, Streptococcus 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 Studies Diagnostic testing studies ↓ all classes of Ig ↓ levels of B-cells normal T-cells Differential Severe combined immunodeficiency distinguishing factor similarly presents with recurrent bacterial infections unlike Bruton agammaglobulinemia, flow cytometry shows absent T-cells Transient hypogammaglobulinemia of infancy distinguishing factor does not extend beyond infancy DIAGNOSIS Diagnostic criteria confirmed with DNA, mRNA, or protein analysis showing mutation in BTK Treatment Management approach mainstay of treatment is to treat each infection with antibiotics First-line intravenous immunoglobulin Complications Small risk of malignancy Prognosis Normal prognosis with regular intravenous immunoglobulin (IVIG) therapy and early detection