What is XLA?

X-linked agammaglobulinemia (a-gam-uh-glob-u-lih-NEE-me-uh) was discovered in 1952 as the first primary immune deficiency. Patients are deficient in the protein Btk leading to an inability to produce antibodies. Antibodies are vital to the human immune system, therefore XLA patients are immune compromised and susceptible to infections.

Overview

XLA is an inherited/genetic immune system disorder that reduces your ability to fight infections. XLA prevents your B cells from reaching full maturation, meaning they are unable to produce their own effective antibodies. People with XLA might get infections of the inner ear, sinuses, respiratory tract, bloodstream and internal organs. XLA affects males almost exclusively, although females can be genetic carriers of the condition. Most people with XLA are diagnosed in infancy or early childhood, after they've had repeated infections. Some people aren't diagnosed until adulthood.

Symptoms

Babies with XLA generally appear healthy for the first few months because they are protected by the antibodies they got from their mothers before birth. When these antibodies clear from their systems, the babies begin to develop often severe, recurrent bacterial infections — such as of the ears, lungs, sinuses and skin — that can be life-threatening.

Male infants born with XLA have:

  • Very small tonsils

  • Small or no lymph nodes

Causes

X-linked agammaglobulinemia is caused by a genetic mutation in a gene called BTK. This gene is needed to produce a protein called Bruton's tyrosine kinase (BTK) which is necessary for B cells to mature into antibody-producing B cells. People with the condition can not produce antibodies that fight infection. About 40% of people with the condition have a family member who has it.

Complications

People with XLA can live relatively normal lives and should be encouraged to participate in regular activities for their ages. However, recurrent infections related to XLA will likely require careful attention and aggressive treatment. They can cause organ damage and be life-threatening.

Possible complications include:

  • Chronic lung disease

  • Increased risk of certain cancers

  • Infectious arthritis

  • Increased risk of central nervous system infections from live vaccines

Diagnosis

A medical history documenting recurrent infections and possible family history is important. This along with a physical examination and blood tests may be enough for a diagnosis. Genetic testing may be recommended to confirm the diagnosis.

Treatment

Currently, there is no cure for XLA. The goal of treatment is to supplement the immune system with antibodies to provide passive immunity.

Medications to treat XLA include:

  • Gammaglobulin. This is a type of protein found in blood that contains antibodies against infections. It's given by infusion into a vein every two to four weeks or by weekly injection.

    Reactions to gammaglobulin can include headache, chills, backache and nausea. Reactions are more likely to occur during a viral infection.

  • Antibiotics. Some people with XLA receive continuous antibiotics to prevent infections. Others take antibiotics for bacterial infections longer than people without XLA do.