X-Linked Agammaglobulinemia

What is X-linked agammaglobulinemia?

X-linked agammaglobulinemia is a genetic disease that causes a weakened immune system. It is also called Bruton's agammaglobulinemia or congenital agammaglobulinemia. "X-linked" means that the gene that causes this disease is located on the X chromosome. It mainly affects males, because they have only have one X chromosome. The disease is rare.

A child with this disease can’t make antibodies that are part of gamma globulins in blood plasma. Antibodies are the body's main defense against germs like bacteria and viruses. So a child with this disease can’t fight off infections caused by bacteria and by some viruses.

Boys with this disease are more likely to get infections in the middle ear, sinuses, and lungs. The infections can also involve the bloodstream or internal organs. Most children with this disease who are treated early are able to lead relatively normal lives.

What causes X-linked agammaglobulinemia?

X-linked agammaglobulinemia is caused by a faulty gene on the X chromosome. Humans normally have 23 pairs of chromosomes in each cell of their body. The 23rd pair governs gender. Females have two X chromosomes, and males have one X and one Y chromosome. Females can have a disease-causing gene on one of their X chromosomes but not have any symptoms of the disease. They are called carriers for the condition. Males only have one X chromosome. So if their X chromosome carries a disease-causing gene, then they will have symptoms. Carrier females have a 1 in 2 chance of passing the X chromosome with the nonworking gene to a child. This is true for every pregnancy. If a daughter gets the gene, she will be a healthy carrier like her mother. If a son gets the gene, he will have X-linked agammaglobulinemia.

A woman can get tested for the gene. If you are a known carrier, you can also have prenatal testing. This might be amniocentesis or chorionic villus sampling.

In some cases, a child may have the faulty gene without inheriting it. It can happen if there is a new change (mutation) on the child’s X chromosome.

What are the symptoms of X-linked agammaglobulinemia?

The symptoms of this disease usually show up in the first 6 to 9 months of age. But they can also show up as late as age 3 to 5 years.

These are the common symptoms:

  • Numerous, serious, or life-threatening illnesses such as infections of the nasal passages, skin, eyes, bones, lungs, digestive tract, and bloodstream.

  • Failure to grow

  • No tonsils or adenoids

  • Joint disease, mainly in the knees, similar to juvenile rheumatoid arthritis

  • Breakdown of red blood cells (autoimmune hemolytic anemia)

  • Kidney inflammation (glomerulonephritis)

  • Fewer white blood cells called neutrophils (neutropenia)

  • Skin and muscle inflammation (dermatomyositis)

A few older children with this disease may have cancers such as leukemia, lymphoma, or colon cancer.

The symptoms of this disease may look like other health conditions. Make sure your child sees his or her healthcare provider for a diagnosis.

How is X-linked agammaglobulinemia diagnosed?

Your child’s healthcare provider will look at your child’s health history and do a physical exam. Your child may need many blood tests to help confirm the diagnosis.

How is X-linked agammaglobulinemia treated?

Treatment will depend on your child’s symptoms, age, and general health. It will also depend on how severe the condition is.

Treatment may include:

  • Replacing antibodies. This treatment gives your child the antibodies that he or she cannot make. This protects your child against infections. It also helps stop infections from spreading.

  • Treating infections. The healthcare provider will treat any infections right away. Or the provider may give your child antibiotics before he has an infection (prophylactically).

  • Not getting any live viral vaccines. This includes vaccines for measles, mumps, rubella (MMR) and chickenpox (varicella). This is because your child could develop the disease the vaccine is meant to protect against.

Long-term outlook for a child with X-linked agammaglobulinemia

Without antibody replacement, a child with this disease could die at an early age from severe infections. Some children who get chronic lung disease with widening and scarring of the airways (bronchiectasis) may have a shortened lifespan. But most children with X-linked agammaglobulinemia who are treated early should be able to lead normal, active lives.