X-linked agammaglobulinemia (XLA) is a rare genetic condition that affects the immune system. It is caused by a variant in a gene called Bruton tyrosine kinase (BTK). Individuals with XLA have a deficiency of B cells, which are responsible for producing antibodies to fight infections. This results in a weakened immune system and an increased susceptibility to recurrent infections.
Individuals with XLA often have frequent respiratory tract infections, such as pneumonia and bronchitis. They may also have recurring ear infections. XLA is typically diagnosed in early childhood, when these infections become more severe and persistent. Genetic testing can confirm the diagnosis by identifying the specific mutation in the BTK gene.
There is currently no cure for XLA, but treatment can help manage the symptoms and prevent infections. This may involve regular infusions of immunoglobulin therapy to provide the missing antibodies. Early diagnosis and treatment are crucial in order to prevent complications and improve the quality of life for individuals with XLA.
It is important for individuals with XLA and their families to seek support and information from advocacy organizations, such as the Immune Deficiency Foundation, which provides resources and educational materials. ClinicalTrials.gov and OMIM (Online Mendelian Inheritance in Man) are valuable sources of information on ongoing research studies and genetic information associated with XLA.
References:
Conley, M. E. (2004). Clinical spectrum of X-linked agammaglobulinemia. Journal of Pediatrics, 144(5 Suppl), S16–S20.
Gene, K. et al. (2009). X-linked agammaglobulinemia: Clinical approach to diagnosis and management—188 Conley lecture. Annals of Allergy, Asthma & Immunology, 103(6), S8–S19.
Frequency
The frequency of X-linked agammaglobulinemia (XLA) is estimated to be 1 in 190,000 to 1 in 1,000,000 males worldwide. It is considered a rare condition.
XLA is caused by mutations in the BTK gene, which is located on the X chromosome. The inheritance pattern of XLA is X-linked, meaning that the gene mutation is passed from a carrier mother to her son. Female carriers of the gene mutation usually do not display symptoms of XLA due to the presence of a second, normal X chromosome.
Diagnosis of XLA is typically confirmed through genetic testing, which identifies mutations in the BTK gene. This testing can be done as part of a comprehensive evaluation of immune system function in children with suspected immunodeficiency.
The frequency of XLA has been studied in various populations. In a study of patients from the Primary Immune Deficiency Treatment Consortium (PIDTC), XLA accounted for 11.3% of all primary immunodeficiency diseases diagnosed in children. Similarly, a study published in Clinical Immunology in 2013 reported that XLA accounted for 6% of all primary immunodeficiency diseases diagnosed in adults.
Information about clinical trials for XLA can be found on the ClinicalTrials.gov website. This website provides a catalog of clinical research studies, including those for XLA. It also lists information about ongoing studies, their testing requirements, and how to participate.
To learn more about XLA, additional information and resources can be found on the Genetic and Rare Diseases Information Center (GARD) website. GARD provides information about rare genetic diseases, including XLA, and offers support for patients and their families.
Scientific articles and research papers about XLA can be accessed through resources such as PubMed and OMIM. These databases provide access to a wide range of scientific publications, including studies on the genetics, causes, and clinical manifestations of XLA.
XLA is also known by other names, including Bruton agammaglobulinemia, Bruton type agammaglobulinemia, X-linked agammaglobulinaemia, X-linked agammaglobulinaemia, and agammaglobulinemia, X-linked.
References:
- Conley ME, Broides A, Hernandez-Trujillo V, et al. Genetic analysis of patients with defects in early B-cell development. Immunol Rev. 2005;203:216–234.
- OMIM Entry – #300755 – AGAMMAGLOBULINEMIA 1, X-LINKED; XLA. Available from: https://omim.org/entry/300755.
- PubMed search results for “X-linked agammaglobulinemia”. Available from: https://pubmed.ncbi.nlm.nih.gov/?term=X-linked+agammaglobulinemia.
- Primary Immune Deficiency Treatment Consortium (PIDTC), McLaughlin LP, Henderson SL, et al. Late-onset X-linked agammaglobulinemia. J Allergy Clin Immunol. 2020;145(2):717–720.e6. doi:10.1016/j.jaci.2019.09.027.
Causes
X-linked agammaglobulinemia is a genetic condition that is caused by mutations in the BTK gene. BTK stands for Bruton’s tyrosine kinase, which is important for the development and function of B cells, a type of white blood cell that produces antibodies. Without functional BTK protein, the B cells cannot mature and produce antibodies normally.
This condition is inherited in an X-linked recessive manner, which means that it primarily affects males. Females can be carriers of the BTK gene mutation, but they usually do not have any symptoms of the condition.
The BTK gene mutations can occur in different locations within the gene, leading to variable severity of the condition. Some mutations may completely eliminate BTK protein function, while others may result in a partial loss of function. The severity of the condition can also be influenced by other genetic factors and environmental factors.
The frequency of X-linked agammaglobulinemia in the population is approximately 1 in 190,000 to 1 in 230,000 males. It is considered a rare disease.
Research on X-linked agammaglobulinemia and related conditions is ongoing, with new discoveries being made about the genetic causes, clinical features, and treatment options. Several scientific articles can be found on PubMed and OMIM, providing more information about the genetic basis of the condition.
Genetic testing is available for diagnosing X-linked agammaglobulinemia. This testing can identify mutations in the BTK gene and confirm the diagnosis. It can also be used for carrier testing in families with a history of the condition.
For patients with X-linked agammaglobulinemia, there are additional resources available for support, advocacy, and information. The Jeffrey Modell Foundation and the Immune Deficiency Foundation are two organizations that provide educational materials, support groups, and other resources for patients and their families.
Studies and clinical trials are also being conducted to explore new treatments and improve the quality of life for individuals with X-linked agammaglobulinemia. ClinicalTrials.gov is a valuable resource for finding information about ongoing studies and clinical trials related to this condition.
In summary, X-linked agammaglobulinemia is a rare genetic condition caused by mutations in the BTK gene. These mutations lead to impaired development and function of B cells, resulting in a lack of antibodies. Genetic testing and resources are available to support patients and their families, and research is ongoing to improve understanding and treatment options for this condition.
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Learn more about the gene associated with X-linked agammaglobulinemia
X-linked agammaglobulinemia is a rare condition that affects the immune system. It is also known as Bruton agammaglobulinemia or XLA. This condition is caused by mutations in the BTK gene, which is located on the X chromosome.
The BTK gene provides instructions for making a protein called Bruton tyrosine kinase (BTK). This protein plays a crucial role in the development and maturation of B cells, which are a type of white blood cell that produces antibodies. Antibodies are essential for the body’s defense against infections.
Individuals with X-linked agammaglobulinemia have a faulty BTK gene, which prevents the production of functional BTK protein. As a result, B cells are unable to develop and mature properly. This leads to a significant reduction in the production of antibodies, leaving affected individuals more susceptible to infections.
Genetic testing is available to diagnose X-linked agammaglobulinemia. The BTK gene can be analyzed to identify mutations or variants that are associated with the condition. This testing can help confirm a diagnosis, determine the genetic cause of the condition, and provide information for genetic counseling.
For more scientific information about X-linked agammaglobulinemia and the BTK gene, additional studies and research articles can be found on PubMed. These articles provide a wealth of information and can help support further understanding of the condition and its genetic basis.
The Genetic Testing Registry (GTR) is another valuable resource for information on genetic testing for X-linked agammaglobulinemia. The GTR catalog provides a comprehensive list of genetic tests available for various conditions, including XLA. It also includes details about the genes involved and their associated variants.
The NORD (National Organization for Rare Disorders) and the Immune Deficiency Foundation are organizations that can provide further support and resources for individuals and families affected by X-linked agammaglobulinemia. They offer information about the condition, research updates, patient support, and opportunities to participate in clinical trials.
In summary, the BTK gene is the main gene associated with X-linked agammaglobulinemia. Mutations or variants in this gene cause a deficiency in antibody production, leading to an increased susceptibility to infections. Learning more about this gene, as well as other genes and cells involved in the immune system, can help support further research, testing, and treatment efforts for individuals with this condition.
Inheritance
X-linked agammaglobulinemia (XLA) is a genetic condition that is inherited in an X-linked recessive manner. This means that the condition primarily affects males, while females can be carriers of the gene mutation and may have milder symptoms or be asymptomatic.
Scientists have identified the genetic variant associated with XLA and named it the Bruton tyrosine kinase (BTK) gene. Mutations in the BTK gene lead to a deficiency in B-lymphocytes, which are responsible for producing antibodies to fight against infections.
Research studies have shown that approximately 85% of XLA cases are caused by mutations in the BTK gene. These mutations can be detected through genetic testing, which is recommended in individuals with a family history or symptoms suggestive of XLA.
The frequency of XLA in the general population is estimated to be 1 in 200,000 to 1 in 1,000,000 live births. However, the condition may be more common in certain populations due to founder effects or consanguinity.
Patients with XLA require lifelong antibody replacement therapy to prevent recurrent infections. Genetic counseling and testing can help affected families understand the inheritance pattern and provide information on the risk of passing the condition to future generations.
For more information on XLA inheritance and support resources, the following websites can be helpful:
- Genetic and Rare Diseases Information Center (GARD)
- Online Mendelian Inheritance in Man (OMIM)
- ClinicalTrials.gov
- PubMed
In addition, articles and studies published in scientific journals, advocacy organizations, and patient support groups can provide further information and support for families affected by XLA and other genetic diseases.
Other Names for This Condition
X-linked agammaglobulinemia is also known by other names, including:
- Bruton-type agammaglobulinemia
- XLA
- Agammaglobulinemia, X-linked
- Agammaglobulinemia type 1
- Bruton agammaglobulinemia
These names are used interchangeably and refer to the same condition. They are all based on the scientific understanding of the condition and its associated genetic causes. Understanding the various names can help patients and their families find more information, connect with support resources, and learn about ongoing research studies.
The condition was first discovered by Dr. Ogden C. Bruton in 1952, hence the name “Bruton-type agammaglobulinemia” or “Bruton agammaglobulinemia.” The term “X-linked” refers to the inheritance pattern of the condition, which is linked to a specific gene on the X chromosome.
X-linked agammaglobulinemia is caused by mutations in the BTK gene, which is responsible for producing a protein necessary for the development and maturation of B cells. B cells are a type of white blood cell that produce antibodies, the proteins responsible for fighting off infections. Without functioning BTK genes, individuals with X-linked agammaglobulinemia are unable to produce adequate amounts of antibodies, leading to recurrent and severe infections.
The condition is relatively rare, occurring in about 1 in 200,000 to 1 in 500,000 live births. It primarily affects males, as the BTK gene is located on the X chromosome, and males have one X chromosome and one Y chromosome. Females have two X chromosomes, so even if one X chromosome carries a mutated BTK gene, the other X chromosome can compensate for its function.
To diagnose X-linked agammaglobulinemia, genetic testing can be performed to identify mutations in the BTK gene. This testing can confirm the diagnosis in individuals with characteristic symptoms and a suspected genetic inheritance pattern. In addition, laboratory tests can be conducted to measure the levels of immunoglobulins (antibodies) and B cells in the blood.
For additional information on X-linked agammaglobulinemia, patients and their families can consult resources like the Online Mendelian Inheritance in Man (OMIM) database, which provides detailed information on genetic diseases, including XLA. PubMed is another valuable resource for scientific articles and research studies related to the condition.
The Jeffrey Modell Foundation and the Immune Deficiency Foundation also provide advocacy, support, and educational resources for individuals and families affected by X-linked agammaglobulinemia and other primary immunodeficiency disorders. These organizations can help connect patients with clinical trials, genetic testing, and other resources to improve the quality of life for individuals with the condition.
References:
- Conley ME. X-Linked Agammaglobulinemia. Immunol Allergy Clin N Am. 2008;28(2):W157-W166.
- X-Linked Agammaglobulinemia. Genetics Home Reference. Retrieved from https://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia
- X-Linked Agammaglobulinemia. National Organization for Rare Disorders (NORD). Retrieved from https://rarediseases.org/rare-diseases/x-linked-agammaglobulinemia/
- X-Linked Agammaglobulinemia. Jeffrey Modell Foundation. Retrieved from https://www.info4pi.org/library/educational-materials/jeffrey-modell-publications/
- Jeffrey Modell Foundation (JMF) Patient & Family Handbook for Primary Immunodeficiencies (6th ed.). Retrieved from https://www.info4pi.org/images/PDFs/JMF_Handbook.pdf
Additional Information Resources
Here are some additional resources to learn more about X-linked agammaglobulinemia:
- PubMed: A database of scientific articles and studies on X-linked agammaglobulinemia and other related diseases. You can find information about the genetic causes, inheritance patterns, clinical trials, and more.
- OMIM: The Online Mendelian Inheritance in Man database provides comprehensive information about genetic disorders, including X-linked agammaglobulinemia. It contains detailed descriptions of the associated genes and variants, as well as clinical and research information.
- ClinicalTrials.gov: This website lists ongoing clinical trials related to X-linked agammaglobulinemia. You can find information about current studies, patient support and advocacy groups, and opportunities for genetic testing and research participation.
- NIAMS Catalog: The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) catalog provides information about X-linked agammaglobulinemia and other rare genetic disorders. You can find articles, research studies, and resources for patients and their families.
Genetic Testing Information
Testing for X-linked agammaglobulinemia is available and can provide valuable information about the genetic cause of this condition. Genetic testing can also help with research studies and provide more information about the genes associated with X-linked agammaglobulinemia.
Genetic testing can be done to identify the specific gene variant that causes X-linked agammaglobulinemia. This testing can be done using a blood sample or other genetic samples to analyze the patient’s genes. The results of genetic testing can help with diagnosis and understanding the inheritance pattern of this condition.
There are several resources available to support individuals and families who are interested in genetic testing for X-linked agammaglobulinemia. These resources include scientific articles, advocacy groups, and patient support organizations. These resources can provide additional information and help individuals learn more about the genetic testing process.
In addition to genetic testing, other laboratory tests can be done to evaluate the immune system of individuals with X-linked agammaglobulinemia. These tests may include measuring antibodies and assessing the function of B-cells. These tests can help clinicians better understand the clinical features and prognosis of individuals with X-linked agammaglobulinemia.
For more information about genetic testing for X-linked agammaglobulinemia, you can refer to the following resources:
- The National Center for Biotechnology Information’s Online Mendelian Inheritance in Man (OMIM) catalog
- The ClinicalTrials.gov database for ongoing research studies
- Peer-reviewed articles from PubMed
- Genetic testing laboratories and centers that specialize in rare diseases
- Support and advocacy groups for X-linked agammaglobulinemia
These resources can provide up-to-date information about genetic testing, gene variants associated with X-linked agammaglobulinemia, and other relevant research studies.
Overall, genetic testing plays a crucial role in understanding the causes of X-linked agammaglobulinemia and improving the quality of patient care. It provides valuable information for both clinicians and individuals affected by this condition.
Genetic and Rare Diseases Information Center
The Genetic and Rare Diseases Information Center (GARD) is a resource provided by the National Institutes of Health. GARD provides reliable, up-to-date, and easy-to-understand information about rare genetic diseases. One such disease covered by GARD is X-linked agammaglobulinemia.
X-linked agammaglobulinemia is a rare genetic condition that primarily affects males. It is characterized by a lack of certain immune system cells called B cells and low levels of antibodies. This condition is caused by mutations in the BTK gene.
GARD offers a variety of resources related to X-linked agammaglobulinemia, including articles about the condition, information about the genes involved, and the frequency of the disease. Additionally, GARD provides links to resources for genetic testing, clinical trials, and scientific studies associated with X-linked agammaglobulinemia. Patient advocacy organizations, such as the Jeffrey Modell Foundation and the Immune Deficiency Foundation, are also listed as additional sources of information and support.
GARD provides comprehensive information on X-linked agammaglobulinemia, including clinical features, inheritance patterns, associated diseases, and genetic testing options. Information on specific variants of the BTK gene, their associated symptoms, and their frequency can also be found on the GARD website.
For scientific and research purposes, GARD offers references to articles published on PubMed, OMIM (Online Mendelian Inheritance in Man), and other reputable scientific sources.
In addition to information about X-linked agammaglobulinemia, GARD provides a range of resources and information on other genetic and rare diseases. The goal of GARD is to help patients, families, healthcare providers, and researchers learn more about these conditions, understand their causes, and access the necessary support and resources.
For more information about X-linked agammaglobulinemia and other rare diseases, visit the Genetic and Rare Diseases Information Center at the following website: https://rarediseases.info.nih.gov.
Patient Support and Advocacy Resources
X-linked agammaglobulinemia (XLA), also known as Bruton’s agammaglobulinemia, is a rare genetic condition caused by a variant in the BTK gene. It predominantly affects males and is characterized by a lack of mature B cells, leading to an inability to produce antibodies. This condition is inherited in an X-linked recessive manner.
Patients with XLA and their families may benefit from additional information and support. The following resources provide valuable information on XLA, genetic testing, clinical trials, and patient advocacy:
- OMIM: OMIM (Online Mendelian Inheritance in Man) is a database that provides comprehensive information about genetic diseases. The OMIM entry for XLA (OMIM #300755) includes references to scientific articles, clinical studies, and genetic information.
- X-Linked Agammaglobulinemia GeneReviews: The GeneReviews website provides in-depth summaries of genetic conditions, including XLA. It offers information on the genetic basis, clinical features, genetic testing, and management of the condition.
- Bruton’s Tyrosine Kinase (BTK) Gene Testing: Genetic testing can confirm the presence of a BTK gene variant associated with XLA. Several laboratories offer BTK gene testing, which can provide a definitive diagnosis for individuals suspected of having XLA.
- ClinicalTrials.gov: ClinicalTrials.gov is a comprehensive database that provides information on clinical trials for various conditions, including XLA. It can help patients and their families find ongoing or upcoming clinical trials related to XLA and explore the possibility of participating in research studies.
- X-Linked Agammaglobulinemia Research Center: Some medical centers and research institutions specialize in studying XLA and other primary immunodeficiency disorders. These research centers can provide valuable information and resources for patients and their families.
- PubMed: PubMed is a widely used database for scientific articles. Searching for “X-linked agammaglobulinemia” on PubMed can provide access to published research papers, review articles, and case reports related to the condition.
- National Organization for Rare Disorders (NORD): NORD is a patient advocacy organization that provides support and resources for individuals with rare diseases, including XLA. Their website offers information on XLA, patient stories, and links to other helpful resources.
- IMMUNOL: IMMUNOL is a comprehensive immunology and allergy research catalog that includes information on genes, antibodies, and other related products. It can be a valuable resource for researchers and healthcare professionals studying XLA and related conditions.
These resources can help patients with XLA and their families learn more about the condition, find additional support, and stay informed about the latest research and advancements in the field. It is important for individuals affected by XLA to connect with advocacy organizations and medical professionals experienced in treating this rare genetic disorder.
Research Studies from ClinicalTrials.gov
In addition to clinical testing for X-linked agammaglobulinemia, there are other research studies available on ClinicalTrials.gov that aim to further our understanding of this genetic condition.
These studies help to improve the quality of care for patients with X-linked agammaglobulinemia by investigating various aspects of the disease, such as its causes, associated genes, and the frequency of its occurrence.
Scientific research studies also help to develop new testing methods and therapies for X-linked agammaglobulinemia. These studies focus on gene testing, identifying gene variants associated with the condition, and studying the function of B cells and antibodies in patients with X-linked agammaglobulinemia.
ClinicalTrials.gov is a valuable resource for individuals and families affected by X-linked agammaglobulinemia. The website provides a catalog of ongoing and completed clinical trials, as well as information on their purpose, eligibility criteria, and contact details for further inquiries.
Additionally, websites such as OMIM (Online Mendelian Inheritance in Man) and PubMed offer articles and references related to X-linked agammaglobulinemia, providing further information on the condition and its genetic basis. Advocacy groups and genetic support centers may also provide additional resources and support for individuals and families affected by X-linked agammaglobulinemia.
By participating in research studies and staying informed about the latest scientific advancements, individuals with X-linked agammaglobulinemia and their families can contribute to the understanding and treatment of this rare genetic condition.
Catalog of Genes and Diseases from OMIM
X-linked agammaglobulinemia (XLA) is a rare genetic condition that affects the body’s ability to produce antibodies, which are essential for the immune system to fight off infections. The main gene associated with XLA is the Bruton’s tyrosine kinase (BTK) gene.
OMIM (Online Mendelian Inheritance in Man) is a comprehensive catalog of genetic variants and associated diseases. It provides a wealth of resources for researchers, clinicians, and patients to learn more about XLA and other genetic diseases.
The OMIM catalog includes information on the genetic causes of XLA, additional genes associated with the condition, and their associated clinical features. It also provides links to other scientific articles, references, and research studies on XLA. This information can help researchers and clinicians better understand the condition and develop improved testing and treatment strategies.
For patients and their families, OMIM provides valuable resources and support. It offers information about genetic testing for XLA, advocacy and patient support organizations, and clinical trials that may be available for the condition. OMIM also provides links to PubMed articles and other quality sources of information on XLA.
By using the resources available on OMIM, researchers, clinicians, and patients can stay informed about the latest advancements in XLA research, testing, and treatment options. These resources can help improve the quality of care for individuals with XLA and provide them with the necessary support they need.
Scientific Articles on PubMed
X-linked agammaglobulinemia (XLA), also known as Bruton’s agammaglobulinemia, is a rare genetic condition that causes a deficiency in B cells, resulting in an inability to produce antibodies. The condition is caused by mutations in the gene named “BTK” (Bruton’s tyrosine kinase), which plays a crucial role in the development of B cells.
Children with XLA are highly susceptible to infections and often experience recurrent respiratory tract infections and other diseases caused by a lack of functional antibodies. XLA is inherited in an X-linked recessive manner, meaning that the gene mutation is located on the X chromosome. Therefore, the condition primarily affects males, while females are carriers of the gene mutation.
Scientific articles on PubMed provide valuable information about XLA, its variant names, associated genes, inheritance patterns, and clinical studies. These articles help researchers, healthcare providers, and advocacy groups learn more about the condition and support patients and their families.
Some of the scientific articles available on PubMed include studies on genetic testing for XLA, the frequency and quality of testing, and the conley gene catalog, which provides information about genes associated with XLA and other genetic diseases. Additionally, articles discuss the role of BTK mutations in XLA and their impact on B cell development and function.
By referencing scientific articles on PubMed, healthcare professionals and researchers can access reliable and up-to-date information about XLA and its genetic causes. These resources are essential for improving the diagnosis, management, and treatment of patients with XLA and other rare genetic conditions.
In summary, PubMed offers a comprehensive collection of scientific articles about X-linked agammaglobulinemia. These articles provide information about the genetic basis of XLA, testing methods, and research studies. Utilizing these resources can help healthcare providers and researchers further understand the condition, better support patients, and enhance the overall quality of care.
References
- Conley ME, Howard V. X-linked agammaglobulinemia. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1236/.
- Genetic Testing Registry (GTR) [Internet]. X-linked agammaglobulinemia. Bethesda (MD): National Library of Medicine (US); 2018-. Available from: https://www.ncbi.nlm.nih.gov/gtr/tests/556230/overview/.
- OMIM [Internet]. Johns Hopkins University; c2005-https://www.omim.org/entry/300300.
- Conley ME, Broides A, Hernandez-Trujillo V, et al. Genetic analysis of patients with defects in early B-cell development. Immunol Rev. 2005;203:216-234.
- Plebani A, Soresina A, Rondelli R, et al. Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study. Clin Immunol. 2002;104(3):221-230.
- Bruton OC. Agammaglobulinemia. Pediatrics. 1952;9(6):722-728.
- Conley ME. X-linked agammaglobulinemia. Defects of B-cell development and function. Immunol Rev. 2000;178:19-29.
- Bach MP, Rispens T, Bemelman FJ, et al. Variation in clinical presentation, immunology, and treatment outcome of agammaglobulinemia patients with BTK mutations. J Allergy Clin Immunol. 2015;136(3):881-883.