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Genetics Home Reference: your guide to understanding genetic conditions
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X-linked agammaglobulinemia

Reviewed February 2015

What is X-linked agammaglobulinemia?

X-linked agammaglobulinemia (XLA) is a condition that affects the immune system and occurs almost exclusively in males. People with XLA have very few B cells, which are specialized white blood cells that help protect the body against infection. B cells can mature into the cells that produce special proteins called antibodies or immunoglobulins. Antibodies attach to specific foreign particles and germs, marking them for destruction. Individuals with XLA are more susceptible to infections because their body makes very few antibodies.

Children with XLA are usually healthy for the first 1 or 2 months of life because they are protected by antibodies acquired before birth from their mother. After this time, the maternal antibodies are cleared from the body, and the affected child begins to develop recurrent infections. In children with XLA, infections generally take longer to get better and then they come back again, even with antibiotic medications. The most common bacterial infections that occur in people with XLA are lung infections (pneumonia and bronchitis), ear infections (otitis), pink eye (conjunctivitis), and sinus infections (sinusitis). Infections that cause chronic diarrhea are also common. Recurrent infections can lead to organ damage. People with XLA can develop severe, life-threatening bacterial infections; however, affected individuals are not particularly vulnerable to infections caused by viruses. With treatment to replace antibodies, infections can usually be prevented, improving the quality of life for people with XLA.

How common is X-linked agammaglobulinemia?

XLA occurs in approximately 1 in 200,000 newborns.

What genes are related to X-linked agammaglobulinemia?

Mutations in the BTK gene cause XLA. This gene provides instructions for making the BTK protein, which is important for the development of B cells and normal functioning of the immune system. Most mutations in the BTK gene prevent the production of any BTK protein. The absence of functional BTK protein blocks B cell development and leads to a lack of antibodies. Without antibodies, the immune system cannot properly respond to foreign invaders and prevent infection.

Related Gene(s)

Changes in this gene are associated with X-linked agammaglobulinemia.

  • BTK

How do people inherit X-linked agammaglobulinemia?

This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

About half of affected individuals do not have a family history of XLA. In most of these cases, the affected person's mother is a carrier of one altered BTK gene. Carriers do not have the immune system abnormalities associated with XLA, but they can pass the altered gene to their children. In other cases, the mother is not a carrier and the affected individual has a new mutation in the BTK gene.

Where can I find information about diagnosis or management of X-linked agammaglobulinemia?

These resources address the diagnosis or management of X-linked agammaglobulinemia and may include treatment providers.

  • Gene Review: X-Linked Agammaglobulinemia (http://www.ncbi.nlm.nih.gov/books/NBK1453)
  • Genetic Testing Registry: X-linked agammaglobulinemia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0221026)
  • MedlinePlus Encyclopedia: Agammaglobulinemia (http://www.nlm.nih.gov/medlineplus/ency/article/001307.htm)

You might also find information on the diagnosis or management of X-linked agammaglobulinemia in Educational resources (http://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about X-linked agammaglobulinemia?

You may find the following resources about X-linked agammaglobulinemia helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for X-linked agammaglobulinemia?

  • agammaglobulinemia
  • Bruton's agammaglobulinemia
  • congenital agammaglobulinemia
  • hypogammaglobulinemia
  • XLA

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about X-linked agammaglobulinemia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding X-linked agammaglobulinemia?

carrier ; cell ; chromosome ; chronic ; congenital ; family history ; gene ; immune system ; infection ; inheritance ; inherited ; maternal ; mutation ; new mutation ; pneumonia ; protein ; recessive ; sex chromosomes ; sinus ; sinusitis ; white blood cells ; X-linked recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Conley ME, Farmer DM, Dobbs AK, Howard V, Aiba Y, Shurtleff SA, Kurosaki T. A minimally hypomorphic mutation in Btk resulting in reduced B cell numbers but no clinical disease. Clin Exp Immunol. 2008 Apr;152(1):39-44. doi: 10.1111/j.1365-2249.2008.03593.x. Epub 2008 Jan 28. (http://www.ncbi.nlm.nih.gov/pubmed/18241230?dopt=Abstract)
  • Gene Review: X-Linked Agammaglobulinemia (http://www.ncbi.nlm.nih.gov/books/NBK1453)
  • Howard V, Greene JM, Pahwa S, Winkelstein JA, Boyle JM, Kocak M, Conley ME. The health status and quality of life of adults with X-linked agammaglobulinemia. Clin Immunol. 2006 Feb-Mar;118(2-3):201-8. Epub 2005 Dec 22. (http://www.ncbi.nlm.nih.gov/pubmed/16377251?dopt=Abstract)
  • López-Herrera G, Vargas-Hernández A, González-Serrano ME, Berrón-Ruiz L, Rodríguez-Alba JC, Espinosa-Rosales F, Santos-Argumedo L. Bruton's tyrosine kinase--an integral protein of B cell development that also has an essential role in the innate immune system. J Leukoc Biol. 2014 Feb;95(2):243-50. doi: 10.1189/jlb.0513307. Epub 2013 Nov 18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/24249742?dopt=Abstract)
  • Plebani A, Soresina A, Rondelli R, Amato GM, Azzari C, Cardinale F, Cazzola G, Consolini R, De Mattia D, Dell'Erba G, Duse M, Fiorini M, Martino S, Martire B, Masi M, Monafo V, Moschese V, Notarangelo LD, Orlandi P, Panei P, Pession A, Pietrogrande MC, Pignata C, Quinti I, Ragno V, Rossi P, Sciotto A, Stabile A; Italian Pediatric Group for XLA-AIEOP. Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study. Clin Immunol. 2002 Sep;104(3):221-30. (http://www.ncbi.nlm.nih.gov/pubmed/12217331?dopt=Abstract)
  • Väliaho J, Smith CI, Vihinen M. BTKbase: the mutation database for X-linked agammaglobulinemia. Hum Mutat. 2006 Dec;27(12):1209-17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16969761?dopt=Abstract)
  • Winkelstein JA, Marino MC, Lederman HM, Jones SM, Sullivan K, Burks AW, Conley ME, Cunningham-Rundles C, Ochs HD. X-linked agammaglobulinemia: report on a United States registry of 201 patients. Medicine (Baltimore). 2006 Jul;85(4):193-202. (http://www.ncbi.nlm.nih.gov/pubmed/16862044?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2015
Published: February 23, 2015