A health condition caused by a mutation (change) in the BTK gene is called X-linked agammaglobulinemia (XLA). This is an inherited condition, meaning the abnormal gene is passed from the biological parents to the biological children. When it occurs, a part of the immune system does not develop properly, which causes you to get sick frequently. Usually, it is diagnosed in men. Healthcare professionals often treat this condition with antibody infusions.
In other words, in people with this abnormal gene, the body does not produce enough B-cells that play an important role in the immune system function. This part of the body produces antibodies that help fight bacteria, viruses, and other germs. In people with XLA, the immune system does not produce antibodies, which leads to frequent illnesses.
Furthermore, those who suffer from XLA usually have absent or underdeveloped lymph nodes, tonsils, and adenoids. Sometimes, this condition is called Bruton’s agammaglobulinemia, congenital agammaglobulinemia, or hypogammaglobulinemia. However, doctors may use hypogammaglobulinemia for another health condition (common variable immunodeficiency or CVID) similar to XLA. In most cases, CVID is less severe, and it is often diagnosed during adulthood, while XLA is identified in infants before the age of 1.
While it is mostly diagnosed in men, it is generally a rare health condition. It affects approximately 1 in 200,000 men worldwide.
Symptoms
Those who develop XLA may also have underdeveloped certain parts of the immune system (for example, tonsils, adenoids, and lymph nodes). As a result, they frequently suffer from bacterial infections, especially during childhood. For example:
- Bronchitis
- Otitis media (an ear infection)
- Pneumonia
- Sinusitis
- Gastrointestinal infections
- Life-threatening infections that affect the central nervous system, bloodstream, and internal organs
- Delays in growth and development
- Joint pain
- Autoimmune hemolytic anemia
- Glomerulonephritis
- Neutropenia
- Dermatomyositis
- Fatigue (extreme tiredness)
- Chronic (long-term) diarrhea
Moreover, people with XLA are at increased risk of getting recurrent viral or fungal infections such as RSV, the flu, or cytomegalovirus.
Causes
This is a genetic disorder in which children get abnormal genes from their biological parents during pregnancy. XLA occurs due to a mutation (change) in the BTK gene. In normal circumstances, it holds instructions that help the body produce B-cells. These cells are involved in the production of antibodies that help the immune system fight infections. When changes in the BTK gene happen, the body cannot make antibodies to fight bacteria, viruses, and other germs. As a result, a person with XLA gets sick frequently.
What Does X-linked Mean?
During pregnancy, the baby gets from each parent two sets of genes (also called chromosomes). These genes contain different instructions that help the body produce proteins and work properly. When the baby receives only one abnormal gene, the body still works properly because it has the second healthy copy. This condition mostly affects men because they have only one X gene.
Normally, women have two X chromosomes, and even if they receive one abnormal X gene, they have the second healthy one that continues to produce mature B-cells.
Risk Factors
There is a factor that significantly increases the risk of developing XLA. It is a family history of the disease.
However, females can also develop XLA when both biological parents carry the abnormal X chromosome. It may pass to the baby during pregnancy. As a result, the baby no longer has healthy X chromosomes, which leads to XLA. When a female receives only one mutated X chromosome, the condition does not occur, but the woman becomes a carrier.
What Are The Potential Complications of X-linked Agammaglobulinemia?
People with this genetic disorder may also experience some complications, especially if they do not get treatment for this condition. Check some examples below:
- Chronic lung disease
- Infections that may spread to other parts of the body (such as the blood or brain)
- Increased risk of certain factors (such as gastric cancer)
- Crohn’s disease
- Ulcerative colitis
This document does not contain all possible complications. You can also talk with your doctor about ways to reduce the risk or prevent complications of XLA.
How to Prevent X-linked Agammaglobulinemia?
If you are concerned about having a child with XLA, you can perform some genetic tests before pregnancy. For more details, discuss it with your healthcare professional.
Diagnosis
Physicians usually diagnose this health condition by performing blood tests to check for abnormal genes and reduced levels of B-cells or antibodies. Sometimes, doctors may perform some imaging tests to check for infections and other complications.
Treatment
Unfortunately, there is no way to cure this genetic disorder. That’s why treatments focus on reducing the symptoms and preventing lifelong complications. Check below some treatments often recommended by doctors for people with XLA:
- Replacement immunoglobulins (RIgG) – During this treatment, doctors give patients IV (intravenous) antibodies. RIgG should be performed once per month.
- Proactive treatment of infections – For people who develop infections, doctors may recommend antibiotics, antiviral medicines, and others.
- Avoid live vaccines – However, those who suffer from XLA cannot get live vaccines because they can make you sick. These include oral polio vaccines, MMR, chickenpox (varicella), and others.
Frequently Asked Questions
What is the difference between XLA and severe combined immunodeficiency (SCID)?
While XLA negatively affects your B-cells, SCID affects T-cells. Generally, both conditions are genetic disorders that affect the ability of the immune system to fight off infections.
What can I expect if I have X-linked agammaglobulinemia?
People with XLA usually should get treatment for the rest of their lives. Moreover, it is very important to get treatment as soon as possible when illnesses occur.
What are the symptoms of agammaglobulinemia?
These include:
- Recurrent infections of the ear, sinus, and lung
- Developmental delays
- Gastrointestinal infections
This document does not contain all possible symptoms of this condition. However, if you experience any of the previous symptoms or any others that cause concerns, immediately contact your doctor. If you have additional questions, ask your healthcare provider.
