X-linked agammaglobulinemia (XLA) is an immune disorder that causes extremely low levels of B cells, which are an important part of the immune system. XLA can put a person at risk of frequent infections.

The immune system is a network of organs and cells that help defend the body against infection. B cells are a type of white blood cell that creates proteins called antibodies, which help the body fight infections.

Primary immune deficiency diseases (PIDDs) are a group of over 200 different disorders that weaken the immune system and make people more likely to develop infections. XLA is a PIDD that causes a person to produce a very low number of B cells. It may also cause the B cells that someone’s body produces to work inefficiently, producing a low number of antibodies.

A note about sex and gender

Sex and gender exist on spectrums. This article will use the terms “male,” “female,” or both to refer to sex assigned at birth. Learn more.

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Antibodies are important proteins that help the body fight infections. B cells are a type of white blood cell that makes antibodies.

XLA is one of the most common forms of PIDD and affects a person’s B cells. The body makes B cells in the bone marrow. If a person has XLA, it prevents their bone marrow from effectively forming mature B cells.

This means that a person with XLA will have extremely low levels of B cells in their blood, causing them to be vulnerable to invasive infections.

XLA is a genetic disorder, meaning it occurs due to a gene alteration. The gene variation that causes XLA is the gene responsible for coding the protein Bruton tyrosine kinase (BTK). This gene is present on the X chromosome, which is why medical professionals refer to the disorder as X-linked.

Studies show that hundreds of different alterations may cause XLA. However, not one single variation is responsible for more than 3% of the known cases of the disorder.

If a male inherits an X chromosome containing an altered BTK gene, they will develop XLA. This is because males only have one X chromosome. If a female inherits an X chromosome containing a BTK gene variant, they are highly unlikely to develop XLA. They will most likely only carry the altered gene.

If a male has XLA, they can pass the gene variant to all of their biological daughters and none of their sons.

XLA causes a person to have an extremely low number of B cells in their body. This means that those with the condition cannot develop all types of antibodies, making it more difficult for them to fight infections.

People with XLA can develop frequent infections of the:

  • throat
  • ears
  • lungs
  • sinuses

Those with XLA can also develop more serious infections in their:

  • blood
  • skin
  • internal organs
  • central nervous system

People with XLA may cope effectively with short-term viral infections. However, the condition causes a person to be very susceptible to chronic viral infections, such as hepatitis.

Those with XLA often have very small tonsils or none at all.

Infants born with XLA are often healthy and display no signs of illness until around 6 to 9 months of age. This is when maternal antibodies are no longer active in their blood.

If an infant develops regular infections, a medical professional may need to follow several steps to diagnose XLA.

First, they should take a thorough medical history. The medical professional will look for a history of recurrent upper respiratory tract infections, including sinusitis and otitis media.

When taking the infant’s medical history, the doctor will speak to the infant’s parent or caregiver to obtain information about their:

  • general health status
  • hospitalizations
  • surgeries
  • past infections
  • vaccinations and vaccination reactions
  • allergies
  • medications

A medical professional may also carry out a thorough physical exam of the infant.

If a healthcare professional suspects the infant has XLA, they may perform a blood test. They will then look to see if the infant’s B cell levels are low, which is a sign that they have XLA. If an infant has very low levels of B cells, a doctor may carry out genetic testing to confirm their XLA diagnosis.

Currently, there is no cure for XLA, so treatments aim to prevent and treat infections relating to the condition. These approaches often include regular immunoglobulin replacement therapy.

Immunoglobulin is a type of antibody present in the blood. People with XLA and other PIDDs may have very low levels of immunoglobulin or immunoglobulin that does not function well.

When carrying out immunoglobulin replacement therapy, a healthcare professional will administer immunoglobulin via an intravenous drip (through a vein) or subcutaneous infusion (under the skin). This immunoglobulin then helps the body prevent and fight infections.

Other treatment options for people with XLA include:

  • antibiotics to treat and prevent bacterial infections
  • nutritional support
  • social support
  • psychological support
  • educational support
  • counseling

Doctors are often able to identify specific microbes that are responsible for infections in people with XLA. They are then able to prescribe specific treatments to help treat infections that these microbes cause.

X-linked agammaglobulinemia (XLA) is a rare genetic immune disorder affecting B cells. B cells are a type of white blood cell responsible for producing antibodies to fight infections. XLA impairs B cell development, leading to extremely low levels of these cells and antibodies. This makes individuals highly susceptible to recurrent and severe infections.

Common infections in people with XLA include infections of the throat, ears, lungs, sinuses, blood, and central nervous system.

Alterations in the Bruton tyrosine kinase (BTK) gene on the X chromosome cause XLA to develop. As such, XLA predominantly affects males due to their single X chromosome. Symptoms typically emerge around 6 to 9 months of age when maternal antibodies are no longer active in the blood.

There is no cure for XLA. Instead, treatment focuses on preventing and managing infections. This involves using immunoglobulin replacement therapy, antibiotics, and supportive care.