National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

X-linked agammaglobulinemia


Other Names:
Bruton type agammaglobulinemia; Bruton's agammaglobulinemia; XLA; Bruton type agammaglobulinemia; Bruton's agammaglobulinemia; XLA; Agammaglobulinemia, BTK; Agammaglobulinemia, Bruton tyrosine kinase; BTK-deficiency See More
Categories:
X-linked agammaglobulinema is a primary immunodeficiency characterized by very low levels of immunoglobulins (proteins made by the immune system to help fight infections). People affected by this condition generally begin developing frequent and recurrent bacterial infections from about 6 months of age. Commonly diagnosed infections include lung infections (pneumonia and bronchitis), middle ear infections, conjunctivitis, sinus infections, various skin infections, and infections that are associated with chronic diarrhea.[1][2][3] X-linked agammaglobulinemia is caused by changes (mutations) in the BTK gene and is inherited in an X-linked recessive manner.[2][3] Treatment aims to boost the immune system, which may be accomplished by administering immunoglobulins through a vein (IVIG) or subcutaneously (SCIG). Frequent infections are generally treated with antibiotics.[1][2]
Last updated: 4/14/2016
Affected infants are usually healthy for the first few months of life until they begin to develop recurrent bacterial infections. The most common bacterial infections are ear infections, pneumonia, pink eye, sinus infections, and infections that cause chronic diarrhea. These bacterial infections can be severe and life-threatening. Most affected individuals are not vulnerable to infections caused by viruses. Infections can usually be prevented with proper treatment.[4]
Last updated: 4/20/2011

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 49 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the tonsils 0100765
Agammaglobulinemia 0004432
Chronic diarrhea 0002028
Chronic otitis media
Chronic infections of the middle ear
0000389
Conjunctivitis
Pink eye
0000509
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Fatigue
Tired
Tiredness
[ more ] 		0012378
Fever 0001945
Glossoptosis
Retraction of the tongue
0000162
Immunodeficiency
Decreased immune function
0002721
Recurrent cutaneous abscess formation 0100838
Recurrent pneumonia 0006532
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Sinusitis
Sinus inflammation
0000246
Skin rash 0000988
Skin ulcer
Open skin sore
0200042
30%-79% of people have these symptoms
Arthritis
Joint inflammation
0001369
Cellulitis
Bacterial infection of skin
Skin infection
[ more ] 		0100658
Hypocalcemia
Low blood calcium levels
0002901
Meningitis 0001287
Neutropenia
Low blood neutrophil count
Low neutrophil count
[ more ] 		0001875
Sensorineural hearing impairment 0000407
Sepsis
Infection in blood stream
0100806
5%-29% of people have these symptoms
Alopecia
Hair loss
0001596
Anemia
Low number of red blood cells or hemoglobin
0001903
Autoimmunity
Autoimmune disease
Autoimmune disorder
[ more ] 		0002960
Hepatitis
Liver inflammation
0012115
Hypopigmented skin patches
Patchy loss of skin color
0001053
Malabsorption
Intestinal malabsorption
0002024
Neoplasm 0002664
Osteomyelitis
Bone infection
0002754
Thrombocytopenia
Low platelet count
0001873
Weight loss 0001824
Percent of people who have these symptoms is not available through HPO
Cor pulmonale 0001648
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay
[ more ] 		0000750
Diarrhea
Watery stool
0002014
Encephalitis
Brain inflammation
0002383
Enteroviral dermatomyositis syndrome 0003729
Enteroviral hepatitis 0001412
Epididymitis 0000031
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Lymph node hypoplasia 0002732
Otitis media
Middle ear infection
0000388
Pneumonia 0002090
Prostatitis
Inflammation of the prostate
0000024
Pyoderma
Pus-filled lesion
0000999
Recurrent urinary tract infections
Frequent urinary tract infections
Repeated bladder infections
Repeated urinary tract infections
Urinary tract infections
Urinary tract infections, recurrent
[ more ] 		0000010
Septic arthritis 0003095
X-linked recessive inheritance 0001419
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Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Managing X-linked agammaglobulinemia (XLA) mainly consists of preventing infections and treating infections aggressively when they do occur. Sudden infections in individuals with XLA are usually treated with antibiotics that are taken for at least twice as long as taken in healthy individuals. Preventing bacterial infections is very important for people with XLA. Gammaglobulin (a type of protein in the blood that contains antibodies to prevent or fight infections) is the main treatment for people with XLA. In the past, most people received this by intravenous (IV) infusion every two to four weeks. However, in the last few years, an increasing number of people have been receiving it by weekly subcutaneous injections. The choice of whether to receive it intravenously or by injection may just depend on what is most convenient for the doctor and/or patient. Sometimes, people with XLA have a reaction to gammaglobulin, which may include headaches, chills, backache, or nausea. These reactions are more likely to occur when they have a viral infection or when the brand of gammaglobulin has been changed. Some centers use chronic prophylactic antibiotics (continuous use of antibiotics) to prevent bacterial infections.[5]

Aggressive use of antibiotics lower the chance of chronic sinusitis and lung disease, which are common complications in individuals with XLA. Early diagnosis and treatment of bowel infections may decrease the risk of inflammatory bowel disease (IBD). Furthermore, children with XLA should not be given live viral vaccines. For example, they should be given inactivated polio vaccine (IPV) rather than the oral polio vaccine. The siblings of children with XLA should also be given inactivated polio vaccine (IPV) rather than oral polio vaccine in order to avoid infecting their affected sibling with live virus.[5]
Last updated: 8/3/2011

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include autosomal recessive or dominant agammaglobulinemia, common variable immunodeficiency (CVID), hyper IgM syndrome and severe combined immunodeficiency (SCID) (see these terms).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to X-linked agammaglobulinemia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with X-linked agammaglobulinemia. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for X-linked agammaglobulinemia:
    United States Immunodeficiency Network (USIDENT) Registry
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on X-linked agammaglobulinemia. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers. 

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss X-linked agammaglobulinemia. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • My child was diagnosed with X-linked agammaglobulinemia in 2008. He as been on antibiotics but now they are no longer effective, and in our country we don't have intravenous immunoglobulin (IVIG). What should I do to keep my child? See answer


  1. Terry W Chin, MD, PhD. Agammaglobulinemia. Medscape Reference. May 2014; http://emedicine.medscape.com/article/884942-overview.
  2. Agammaglobulinemia: X-Linked and Autosomal Recessive. Immune Deficiency Foundation. http://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/agammaglobulinemia-x-linked-autosomal-recessive/. Accessed 4/14/2016.
  3. X-linked agammaglobulinemia. Genetics Home Reference. February 2015; https://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia#definition.
  4. X-linked agammaglobulinemia. Genetics Home Reference. September 2008; http://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia. Accessed 4/20/2011.
  5. Mary Ellen Conley, Vanessa C Howard. X-Linked Agammaglobulinemia. GeneReviews. July 30, 2009; http://www.ncbi.nlm.nih.gov/books/NBK1453/. Accessed 8/3/2011.