iCliniq Logo
HomeHealth articlesGeneral Medicinebruton agammaglobulinemia
Genetic Disorders

Pediatric Bruton Agammaglobulinemia - Causes, Symptoms and Prevention.

Verified data
0

4 min read

Share

Outline

Pediatric Bruton agammaglobulinemia is an inherited genetic disorder characterized by X-linked agammaglobulinemia. Read the article to know more.

Written byDr. Kriti Singh

Medically reviewed byDr. Mohammad Rajja

Published At November 10, 2022
Reviewed AtJuly 23, 2024

What Is X-Linked Agammaglobulinemia?

The first immunodeficiency disease ever identified, X-linked agammaglobulinemia, is caused by a gene on the X chromosome that prevents the production of antibodies. Children with this disease are susceptible to infections in the middle ear, sinuses, and lungs, and it can also affect the bloodstream and internal organs. Also known as Bruton's agammaglobulinemia or congenital agammaglobulinemia, this inherited disorder primarily affects boys, preventing them from producing antibodies, which are crucial for defending the body against bacteria and viruses. This immunodeficiency makes it difficult for affected children to combat bacterial and certain viral infections. Approximately one in 10,000 children are born with this condition. Early diagnosis and treatment can help these children live relatively normal, active lives.

How Do X-linked agammaglobulinemia and Severe Combined Immunodeficiency (Scid) Differ?

The difference between X-linked agammaglobulinemia (XLA) and severe combined immunodeficiency (SCID) lies in the type of immune cells affected. XLA impacts B-cells, whereas SCID affects T-cells. Both conditions are genetic, impair the immune system, and cause frequent illnesses.

What Are the Causes of Pediatric Bruton Agammaglobulinemia?

Pediatric Bruton agammaglobulinemia is a genetic disease. The Bruton tyrosine kinase gene responsible for forming B lymphocytes is mutated, so B lymphocytes are unable to produce antibodies. The child has very small tonsils and lymph nodes. A gene on the X chromosome is mutated. People have 23 pairs of chromosomes in each cell of the body. The 23rd pair controls the person's gender. The pairs X and Y are for males.

In females, the faulty pair of this gene is on one of their X chromosomes. They are the carriers of these genes. Females do not have any symptoms. In males, there is only one X chromosome, so they are symptomatic if there is any carrier gene. In this disease, the Bruton tyrosine kinase (BTK) gene fails to develop in B cells from the pro-B to the pre-B stage. This leads to a significantly reduced number of circulatory B cells and serum immunoglobulins. In some cases, the child can have a faulty gene without inheritance. This happens due to the child's X chromosome mutation before birth.

Which Children Are at Risk of Pediatric Bruton Agammaglobulinemia?

Children whose mothers have carrier genes are at high risk of developing this disease. The mother can pass a faulty X chromosome to a newborn. If it is a girl child, she will be a carrier; if it is a boy child, he will have X-linked pediatric Bruton agammaglobulinemia.

What Are the Symptoms of Pediatric Bruton Agammaglobulinemia?

It is characterized by low levels or absence of immunoglobulins, resulting in recurrent infections.

The symptoms of this disease are usually seen in the first six to nine months. They can also manifest for up to three to five years.

  1. Nasal infections.

  2. Skin infections.

  3. Muscle inflammation.

  4. Breakdown of red blood cells causing (autoimmune hemolytic anemia).

  5. Bone infection.

  6. Eyes and nose infection.

  7. Infection of the bloodstream causes sepsis.

  8. Gastrointestinal infections cause diarrhea.

  9. Retarded growth.

  10. The disease of joints, primarily knees.

  11. Inflammation of the kidney.

  12. Absence of tonsils.

  13. Viral and bacterial infections.

  14. Pneumonia, meningitis, and bronchitis.

  15. Neutropenia.

  16. Cancer such as leukemia, lymphoma, or colon cancer.

What Are the Complications of Pediatric Bruton Agammaglobulinemia?

Due to the absence of antibody formation in a child's body, the disease can be very severe. Children are at high risk of developing blood-borne bacterial infections. Pneumonia can be fatal in this condition. Other complications are bacterial septicemia and meningitis. The patient suffers from severe gastrointestinal infections and pulmonary infections. Chronic sinopulmonary infections include various symptoms of postnasal discharge, tympanic membrane perforation, bronchiectasis, and digital clubbing. Other complications are pneumonia, acute otitis media, septic arthritis, urinary tract infection, and encephalitis.

How Is Pediatric Bruton Agammaglobulinemia Diagnosed?

Diagnosis is confirmed by the child's symptoms and family history.

  • Absent B Cells and Reduced Immunoglobulin Level - Diagnosis is confirmed by detecting the low levels of immunoglobulin, typically IgG, IgA, and IgM, and the absence of B cells. Flow cytometry is used to detect CD19 cells—the presence of transient neutropenia.

  • Genetic Testing - Genetic testing is used to confirm a diagnosis. It is usually recommended if the mutation is identified in family members; mutational analysis of chorionic villus, amniocentesis, and percutaneous umbilical blood samples can confirm the diagnosis.

How Is Pediatric Bruton Agammaglobulinemia Treated?

Treatment of pediatric Bruton agammaglobulinemia depends upon the symptoms of the child. It relies on the severity of the disease.

Treatment includes,

  • Replacing Antibodies - The child is unable to make antibodies against infection. Therefore, the administration of antibodies protects the child from infection. It also helps in stopping the infection from spreading. Aggressive treatment with an antibiotic may prevent severe complications.

  • Treating and Preventing Infections - Proper care should be taken if a child is susceptible to any particular infection. The child should be reported to health care immediately if symptoms are seen.

How Can One Prevent the Occurrence of Pediatric Bruton Agammaglobulinemia?

Genetic tests and counseling can prevent babies from being born with pediatric Bruton agammaglobulinemia. If X-linked agammaglobulinemia runs in families, women should undergo genetic testing before conceiving. They can also undergo prenatal testing to determine if the child has inherited that gene. This can be done through various procedures, such as amniocentesis or chorionic villus sampling.

What Should Parents Do if Their Child Has Pediatric Bruton Agammaglobulinemia?

Parents should report to their pediatrician immediately if the child has symptoms that are not getting better.

  • Fever.

  • Breathing problem.

  • Any discharge from the ear, eyes, or nose.

Apart from all the prevention and precautions, parents should regularly keep appointments with their child's pediatrician. They should try to prevent habits like handwashing and keep the child away from infectious environments. Parents should also inform school management of their child's health status.

Conclusion

Pediatric Bruton agammaglobulinemia is a very common and challenging disease pediatricians encounter in clinical practice. The overall prognosis of this disease is good as long as the patient is diagnosed. Treatment and proper care are required to reduce the sequelae of recurrent infections. Early diagnosis with immediate initiation of treatment can ensure good outcomes. Joint efforts of parents and pediatricians are required for proper management.

Listen to related tracks in our music library

Frequently Asked Questions

To test for Bruton's agammaglobulinemia, a blood test is typically performed to measure the levels of immunoglobulins (antibodies) in the blood. Individuals with the condition have lower levels of immunoglobulins, which makes them more susceptible to recurrent infections. Genetic testing can also be done to identify mutations in the BTK gene, which is responsible for producing a protein critical for the development of B cells, a type of white blood cell involved in antibody production.
Bruton's disease, or X-linked agammaglobulinemia, is caused by a mutation in the BTK gene located on the X chromosome. The mutation affects the production of a protein necessary for developing B cells, which play a crucial role in the immune system by producing antibodies to fight infections. As a result, individuals with Bruton's disease have significantly reduced levels of immunoglobulins, leaving them more susceptible to bacterial infections, particularly of the respiratory tract, ears, and sinuses.
Agammaglobulinemia is a relatively rare condition, with an estimated incidence of 1 in 100,000 to 1 in 200,000 live births. The condition is more common in males, as it is caused by mutations in the X-linked BTK gene. However, some forms of agammaglobulinemia can be inherited autosomal recessive, affecting males and females equally. The condition's prevalence may be higher in certain populations due to increased consanguinity.
Agammaglobulinemia is primarily caused by genetic mutations in genes involved in the development and maturation of B cells, a type of white blood cell responsible for producing antibodies. As such, the condition is considered an inherited disorder transmitted in an X-linked or autosomal recessive manner. In rare cases, agammaglobulinemia may also be acquired later in life due to other underlying medical conditions or certain medications.
Agammaglobulinemia affects the body's ability to produce effective antibodies to fight off infections, which can result in recurrent and severe bacterial infections. Common sites of infection include the respiratory tract, ears, sinuses, and skin. Individuals with agammaglobulinemia may also be susceptible to opportunistic infections, such as Pneumocystis jirovecii pneumonia, and may have an increased risk of developing autoimmune disorders and certain types of cancer.
Yes, Bruton's agammaglobulinemia is a congenital disorder that is inherited in an X-linked recessive manner. This means that the mutation in the BTK gene responsible for the condition is located on the X chromosome, one of the two sex chromosomes. As males have only one X chromosome, a single copy of the mutation is enough to cause the disorder. In females who have two X chromosomes, the presence of one normal copy can partially compensate for the mutation, leading to milder symptoms or even asymptomatic carriers.
No, hypogammaglobulinemia is not a type of leukemia. While both conditions can involve low levels of antibodies and an increased risk of infection, they have different underlying causes and pathologies. Hypogammaglobulinemia refers to a group of primary immunodeficiency disorders characterized by decreased levels of immunoglobulins (antibodies) in the blood, which can be caused by genetic mutations affecting B cells or their precursors. Leukemia, on the other hand, is a group of blood cancers that affect the bone marrow and blood cells, causing abnormal growth and proliferation of white blood cells.
Yes, agammaglobulinemia is considered a primary immunodeficiency disorder, which means that it is caused by inherent defects in the immune system's development or function rather than being a result of external factors such as infections or environmental exposures. Specifically, agammaglobulinemia is caused by genetic mutations that affect the development and maturation of B cells, leading to a deficiency or absence of functional antibodies. This can result in increased susceptibility to recurrent and severe bacterial infections.
No, agammaglobulinemia is not an autoimmune disease. While both conditions involve dysregulation of the immune system, they have different underlying mechanisms and manifestations. Autoimmune diseases occur when the immune system mistakenly attacks the body's tissues, leading to inflammation and tissue damage. In contrast, agammaglobulinemia is caused by a deficiency or absence of functional antibodies, which impairs the body's ability to fight off infections. However, individuals with agammaglobulinemia may have an increased risk of developing autoimmune disorders, possibly due to a loss of regulatory B cells that help prevent autoimmunity.
Agammaglobulinemia is primarily an inherited disorder passed down in families through genetic mutations that affect the development and function of B cells. The condition follows an X-linked recessive inheritance pattern, which means it typically affects males more frequently and severely than females, who are carriers of the mutated gene. However, in rare cases, agammaglobulinemia can also be inherited in an autosomal recessive or dominant pattern, affecting males and females equally or differently depending on the specific gene mutation.
Agammaglobulinemia can be diagnosed through clinical evaluation, laboratory tests, and genetic testing. A diagnosis typically involves assessing the patient's medical history, symptoms, and susceptibility to recurrent bacterial infections and conducting blood tests to measure immunoglobulin levels and B cell counts. Genetic testing may also be performed to identify mutations in the BTK gene associated with X-linked agammaglobulinemia. Additionally, imaging studies and other tests may be done to evaluate the extent and severity of infections or complications related to agammaglobulinemia.
Source Article IclonSourcesSource Article Arrow
Dr. Mohammad Rajja from iCliniq
Dr. Mohammad Rajja

General Practitioner

Consult this doctor

Rate this article

Tags:

bruton agammaglobulinemia

Related topics

Primary B-Cell Disease - Types, Diagnosis, and Treatment

Agammaglobulinemia - Types, Causes, Symptoms, Diagnosis, and Treatment

Ask your health query to a doctor online

General Medicine

*guaranteed answer within 4 hours

Trustpilot

Disclaimer: No content published on this website is intended to be a substitute for professional medical diagnosis, advice or treatment by a trained physician. Seek advice from your physician or other qualified healthcare providers with questions you may have regarding your symptoms and medical condition for a complete medical diagnosis. Do not delay or disregard seeking professional medical advice because of something you have read on this website. Read our Editorial Process to know how we create content for health articles and queries.