Bruton's agammaglobulinemia is an X-linked defect characterized clinically by recurrent sinopulmonary bacterial infections occurring beginning around 6 months of life, when maternally-derived IgG levels wane.
Bruton's agammaglobulinemia, also called X-linked agammaglobulinemia, is one of several genetic B-cell deficiencies that lead to defects in humoral immunity due to faulty B-cell production or differentiation. Others include common variable immunodeficiency syndrome (CVID) and selective IgA deficiency. In Bruton's the defect lies in Bruton's tyrosine kinase (BTK), leading to decreased B-cell differentiation and immunoglobulin production. Typical patients are male and beginning around 6 months of age have recurrent otitis media, pneumonia, sinusitis, conjunctivitis, and giardiasis (due to lack of GI mucosal IgA).
Cooper et al. review primary immunodeficiency disorders (PID) and explain that though PID is usually diagnosed in early childhood, diagnosis in early adulthood is possible with milder forms of disease. They list clinical signs that should raise concern for immunodeficiency including eight or more ear infections in a year, two or more serious sinus or pulmonary infections in a year, patients who have unusual infections, or require IV antibiotics.
Subbarayan et al. conducted a retrospective study of 563 children diagnosed with PID at two centers and concluded that family history of immunodeficiency, history of IV antibiotics for sepsis, and failure to thrive predicted 96% of patients with neutrophil and complement deficiencies and 89% of children with T-cell deficiencies. However, family history was the only predictive factor associated with the genetic B-cell deficiencies.
Illustration A is a diagram of immune cell development with PID-causing defects labeled.
Illustration B is a suggested diagnostic pathway for suspected cases of Bruton's agammaglobulinemia.
Answer 1: Recurrent sinopulmonary infections as well as progressive clumsiness with walking is suggestive of ataxia-telangectasia syndrome, wherein defects in the ATM gene for DNA repair lead to B and T-cell deficiency.
Answer 2: Hypocalcemia and viral infections suggest a diagnosis of DiGeorge syndrome, where T-cell deficiency may result due to an absent thymus.
Answer 3: Oral candidal infection alone may suggest chronic mucocutaneous candidiasis, caused by T-cell dysfunction, with onset usually by 2 years of age.
Answer 5: Bruising, eczema, and recurrent sinopulmonary infections beginning early in life suggest Wiskott-Aldrich syndrome, an X-linked defect in B- and T-cell cytoskeletons leading to loss of both cellular and humoral response.
Cooper MA, Pommering TL, Korányi K. Primary immunodeficiencies. Am Fam Physician. 2003 Nov 15;68(10):2001-8. Review. PubMed PMID: 14655810
PMID:14655810 (Link to Abstract)
Subbarayan A, Colarusso G, Hughes SM, Gennery AR, Slatter M, Cant AJ, Arkwright PD. Clinical features that identify children with primary immunodeficiency diseases. Pediatrics. 2011 May;127(5):810-6. doi: 10.1542/peds.2010-3680. Epub 2011 Apr 11. PubMed PMID: 21482601.
PMID:21482601 (Link to Abstract)