Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ INTRODUCTION ++ Primary immune deficiency diseases (PIDDs) are characterized by an increased susceptibility to infections, often associated with autoimmunity and inflammation, and an increased risk of malignancies because of impaired immune homeostasis and surveillance. Clinical presentation varies depending on the nature of the immune defect. The principal clinical features of PIDDs are listed in Table 51–1. With the exception of immunoglobulin (Ig) A deficiency and DiGeorge syndrome, PIDDs are generally rare, with a prevalence of approximately 1 in 10,000 to 50,000 individuals. Most forms follow Mendelian inheritance and present in childhood; however, some, such as common immunodeficiency, have a multifactorial origin and appear later in life. The diagnostic approach is based on a detailed family and clinical history, physical examination, and appropriate laboratory tests. Laboratory results should be compared with age-matched control values because white blood cell counts, lymphocyte subsets, complement components, Ig levels, and antibody production (especially to polysaccharide antigens) undergo significant changes and progressive maturation in the first years of life. Recognition of PIDDs is essential to start optimal therapies at an early age. ++Table Graphic Jump LocationTABLE 51–1PRINCIPAL CLINICAL FEATURES OF PRIMARY IMMUNODEFICIENCY DISORDERSView Table||Download (.pdf) TABLE 51–1 PRINCIPAL CLINICAL FEATURES OF PRIMARY IMMUNODEFICIENCY DISORDERS Neutrophil Numerical or Functional Defects (Chaps. 63 and 64) Antibody Deficiencies Combined Immune Deficiencies Complement Deficiencies Disorders of Immune Dysregulation Severe bacterial and fungal infections Recurrent bacterial infections after 4–6 months of age Early-onset respiratory and gut infections (bacterial, viral, fungal) Recurrent or severe infections sustained by encapsulated pathogens Variable (depending on the underlying defect) Skin or deep bacterial and fungal abscesses Intestinal Giardia lamblia infection Opportunistic infections Recurrent Neisseria meningitidis infections Bacteria, Candida, spp, Herpesviridae Infections sustained by unusual bacteria and fungi Enteroviral meningoencephalitis Persistent candidiasis Autoimmune manifestations (SLE-like) Lymphocytic interstitial lung disease Colitis Erythroderma aHUS Autoimmune cytopenias Growth failure Recurrent angioedema (C1-INH deficiency) Enteropathy Lymphoproliferation, lymphomas aHUS, atypical hemolytic uremic syndrome; SLE, systemic lupus erythematosus. +++ PREDOMINANT ANTIBODY DEFICIENCIES +++ X-Linked and Autosomal Recessive Agammaglobulinemia +++ Definition and Genetic Features ++ This deficiency is caused by a maturation defect in B-cell development. X-linked agammaglobulinemia (XLA) is the result of a mutation in the Bruton tyrosine kinase (BTK) gene. Autosomal recessive agammaglobulinemia is the result of mutations in genes relevant to immunoglobulin (Ig) heavy or light chains (ie, IGHM, IGLL1, CD79a, CD79b, or the B-cell adaptor molecule, BLINK). +++ Clinical Features ++ XLA and autosomal recessive agammaglobulinemia have similar clinical features: low Ig levels, decreased B cells, and recurrent infections. Normal levels of IgG at birth are a result of transfer from maternal circulation. Thus, affected individuals are usually asymptomatic for the first few months of life. Symptoms and signs vary and may be mild or severe. The condition first develops between 4 and ... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.