X-Linked Agammaglobulinemia

What is X-linked agammaglobulinemia?

X-linked agammaglobulinemia (pronounced “ay-ga-muh-glaa-byou-luh-NEE-mee-uh”), or XLA, is a genetic condition where your body doesn’t make enough mature B-cells. B-cells are an important part of your immune system. They make proteins (antibodies) that help you fight off illnesses. People with XLA aren’t able to fight off illnesses easily and get sick often.

Because B-cells are important for developing certain immune system tissues, people with XLA often have underdeveloped or absent lymph nodes, tonsils and adenoids. Because of how you inherit it, it almost always affects boys or people assigned male at birth (AMAB).

XLA is also called:

• Bruton’s agammaglobulinemia.
• Congenital agammaglobulinemia.
• Hypogammaglobulinemia.

Hypogammaglobulinemia is also a name used for common variable immunodeficiency (CVID), a condition similar to XLA. CVID is usually less severe and typically not diagnosed until adulthood. Providers typically diagnose people with XLA before the age of 1 or as young children.

What’s the difference between X-linked agammaglobulinemia and severe combined immunodeficiency (SCID)?

The difference between X-linked agammaglobulinemia and severe combined immunodeficiency (SCID) is that XLA affects your B-cells, and SCID affects your T-cells. Both are genetic conditions that affect your immune system and make you get sick frequently.

How common is X-linked agammaglobulinemia?

X-linked agammaglobulinemia is rare. It’s more common in babies and kids AMAB. Approximately 1 in 200,000 male babies are born with XLA.

What are the symptoms of X-linked agammaglobulinemia?

People with X-linked agammaglobulinemia usually have small or missing lymph nodes, tonsils and adenoids due to their underdeveloped immune systems. They experience frequent bacterial infections in childhood, including:

• Bronchitis.
• Ear infections (otitis media).
• Sinusitis.
• Pneumonia.
• Gastrointestinal infections.

Children with XLA usually aren’t more likely to get recurrent viral or fungal infections, like cytomegalovirus, RSV or the flu.

What causes X-linked agammaglobulinemia?

XLA is a genetic illness you inherit from one or both biological parents. A change, or mutation, in your BTK gene causes it. This gene gives the instructions that tell your body how to make B-cells. B-cells make antibodies, an important part of your immune system that fights illness.

Changes in your BTK gene mean you can’t fight off illness the same way someone without the mutation can. This means you get sick frequently, sometimes with life-threatening illnesses.

What does X-linked mean?

We all get two sets of genes — one from each parent — in sets called chromosomes. Genes give our bodies instructions on how to make the proteins that keep our bodies working. Often, if there’s a change in one gene, having a second copy makes up for it, so your body can still function properly.

One pair of genes, the sex chromosomes, is mismatched in boys and people AMAB. They have one X and one Y (girls and people assigned female at birth have two Xs). If one of these genes has a mutation, they don’t have another one to compensate for it.

The BTK gene is on the X chromosome (X-linked). Females and people AFAB can have one X chromosome with the mutation that causes XLA but still make enough mature B-cells because they have another functioning copy of BTK. Males and people AMAB only have one X chromosome. If they have a mutation in their BTK, they’ll have XLA.

What are the risk factors for X-linked agammaglobulinemia?

Having a family history of XLA is the only known risk factor.

Can girls have XLA?

Yes, it’s possible. But both parents would have to carry an X chromosome with the mutated BTK gene. Women and people AFAB can be carriers of the gene mutation and pass it on to their children, who might have XLA.

What are the complications of XLA?

Complications of X-linked agammaglobulinemia include:

• Chronic lung disease.
• Infections that spread to other parts of your body, like your blood or your brain.
• Possible increased risk of certain cancers.

How is X-linked agammaglobulinemia diagnosed?

A healthcare provider can perform blood tests to determine whether you or your child have XLA. If test results show a low level of B-cells or antibodies, they’ll do genetic testing to look for DNA changes.

How is X-linked agammaglobulinemia treated?

There’s no cure for XLA. But treatments can help you or your child avoid serious illness. They include:

• Replacement immunoglobulins (RIgG). Your healthcare provider gives you donor antibodies in a vein. You’ll need this treatment at least once per month.
• Proactive treatment of infections. Your provider will treat bacterial infections with antibiotics as soon as they think you’re sick.
• Avoiding live vaccinations. People with XLA can’t get vaccinated with live versions of vaccines, which can make them sick or even be fatal. This includes MMR, chickenpox (varicella) and oral polio vaccines.

Can X-linked agammaglobulinemia be prevented?

If you’re concerned about XLA, a healthcare provider can screen you for genetic conditions you could pass on to your child. If you’re a woman or person AFAB and a carrier of the mutation that causes XLA, you have a 50% chance of passing the mutation to a son, who would have XLA. If you have XLA and are a man or person AMAB, your daughters would be carriers. A genetic counselor or the provider who ordered the testing can advise you on your options if you’re a carrier or have XLA.

What can I expect if I have X-linked agammaglobulinemia?

People with XLA need treatment for the rest of their lives so they’re less vulnerable to illness. They’ll need to work closely with their healthcare provider to treat any illnesses as soon as possible. You or your child can expect to miss more days of school and work due to illness than others.

How long do people with X-linked agammaglobulinemia live?

Thanks to advances in treatment, people with XLA live into adulthood in developed countries like the U.S. In still-developing countries, getting a diagnosis and treatment is much harder. This usually means children with XLA don’t live as long.

How do I take care of myself?

The best way to take care of yourself with XLA is to prioritize your care. Keep appointments with your provider, and make sure you can recognize signs of an infection. Ask your provider what to do if you have symptoms of an infection.

When should I see my healthcare provider?

Talk to a healthcare provider if:

• Your child gets sick from a live vaccine (this includes the MMR vaccine and chickenpox vaccine).
• Your child frequently gets sick with bacterial infections.
• You frequently get sick with bacterial infections.

A provider can tell you whether they need to look into it more.

What questions should I ask my doctor?

It might be helpful to ask a healthcare provider:

• What signs and symptoms of infection should I look for?
• What should I do if I think I or my child have an infection?
• What are the treatment options?
• How often do I or my child need treatment?

A note from Cleveland Clinic

It’s common for kids to get sick frequently. But if your child often gets bacterial infections, something more might be going on. Talk to your provider about concerns you have. Getting a diagnosis and treatment early leads to the best possible outcomes.

If you’re living with XLA — a genetic condition where your body doesn’t make enough mature B-cells — follow your healthcare provider’s guidance about when you may need care. It’s important that you can recognize signs of an infection so you can get treated as soon as possible.