(See also Overview of Immunodeficiency Disorders Overview of Immunodeficiency Disorders Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more and Approach to the Patient With an Immunodeficiency Disorder Approach to the Patient With Suspected Immunodeficiency Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more .)
X-linked agammaglobulinemia is a primary immunodeficiency disorder Primary Immunodeficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more that involves humoral immunity deficiencies Humoral immunity deficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more . It results from mutations in a gene on the X chromosome that encodes Bruton tyrosine kinase (BTK). BTK is essential for B-cell development and maturation; without it, maturation stops before the B-cell stage, resulting in no mature B cells and hence no antibodies.
As a result, male infants have very small tonsils and do not develop lymph nodes; they have recurrent pyogenic lung, sinus, and skin infections with encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae). Patients are also susceptible to persistent central nervous system (CNS) infections resulting from live-attenuated oral polio vaccine and from echoviruses and coxsackieviruses; these infections can also manifest as progressive dermatomyositis Autoimmune Myositis Autoimmune myositis is characterized by inflammatory and degenerative changes in the muscles (polymyositis, necrotizing immune-mediated myopathy) or in the skin and muscles (dermatomyositis)... read more 
with or without encephalitis. Risk of infectious arthritis Acute Infectious Arthritis Acute infectious (septic) arthritis is a joint infection that evolves over hours or days. The infection resides in synovial or periarticular tissues and is usually bacterial—in younger adults... read more 
, bronchiectasis Bronchiectasis Bronchiectasis is dilation and destruction of larger bronchi caused by chronic infection and inflammation. Common causes are cystic fibrosis, immune defects, and recurrent infections, though... read more 
, and certain cancers is also increased.
With early diagnosis and appropriate treatment, prognosis is good unless viral infections of the central nervous system develop.
Diagnosis of X-linked Agammaglobulinemia
Low immunoglobulin levels and absent B cells
Genetic testing
Diagnosis of X-linked agammaglobulinemia is by detecting low (at least 2 standard deviations below the mean) levels of immunoglobulins (IgG, IgA, IgM) and absent B cells (< 1% of all lymphocytes are CD19+ cells, detected by flow cytometry). Transient neutropenia may also be present.
Genetic testing can be used to confirm a diagnosis but is not required. Genetic testing is usually recommended for 1st-degree relatives. If the mutation has been identified in family members, mutational analysis of chorionic villus Chorionic Villus Sampling All procedures used to diagnose genetic disorders, except ultrasonography, are invasive and involve slight fetal risk. If testing detects a serious abnormality, the pregnancy can be terminated... read more , amniocentesis Amniocentesis All procedures used to diagnose genetic disorders, except ultrasonography, are invasive and involve slight fetal risk. If testing detects a serious abnormality, the pregnancy can be terminated... read more , or percutaneous umbilical cord blood Percutaneous Umbilical Blood Sampling All procedures used to diagnose genetic disorders, except ultrasonography, are invasive and involve slight fetal risk. If testing detects a serious abnormality, the pregnancy can be terminated... read more samples can provide prenatal diagnosis.
Treatment of X-linked Agammaglobulinemia
Immune globulin replacement therapy
Treatment of X-linked agammaglobulinemia is immune globulin replacement therapy Replacement of missing immune components Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more .
Prompt use of adequate antibiotics for each infection is crucial; bronchiectasis may require frequent rotation of antibiotics. Live-virus vaccines are contraindicated.
