Overview
X-linked agammaglobulinemia (a-gam-uh-glob-u-lih-NEE-me-uh) is a rare condition that makes it hard to fight infections. The immune systems of people with this condition make very few disease-fighting proteins called antibodies.
X-linked agammaglobulinemia (XLA) is usually an inherited condition. This means it's passed down through families. XLA most often affects males.
XLA is usually diagnosed during infant or toddler years after a child has had repeat illnesses caused by germs. The main treatment uses antibodies from healthy donors to help the body fight infections.
XLA is one of several conditions called primary immunodeficiencies.
Symptoms
Most babies with XLA appear healthy for the first few months. A child is protected by antibodies from the mother before birth and for a few months after birth. When those antibodies break down, the child's body isn't able to make its own.
From 3 to 18 months, illnesses caused by germs may happen more often. These infectious diseases may be severe, long-lasting or difficult to treat. Illnesses of children with XLA can include:
- Ear infections.
- Sinus infections.
- Strep throat.
- Pneumonia.
- Infections or parasites in the digestive system.
- Infections in the bloodstream.
- Infections of the skin or other organs.
People with XLA also may have very small disease-fighting tissues, including:
- Tonsils.
- Adenoids.
- Glands in the neck called lymph nodes.
These tissues are small because they lack the cells that make antibodies.
Causes
XLA is caused by a change in a gene called a mutation. Genes are like sentences in the body's instruction manual. A mutation is like a misspelled word in a sentence that changes how cells are put together or how they work.
The XLA-related gene mutation causes the body to make very few mature white blood cells called B cells. Mature B cells make proteins called antibodies. Antibodies target bacteria, viruses, fungi and parasites that can cause diseases. With few or no B cells, there are almost no antibodies. Without antibodies, the body cannot fight infections.
The gene mutation that causes XLA is on the X chromosome. Typically, a male gets one X chromosome from the mother and one Y chromosome from the father. A female typically gets two X chromosomes, one from each parent.
The most common pattern of inheritance of XLA is that a boy gets an XLA gene mutation on the X chromosome from his mother. Having this one mutation causes the condition.
A girl may inherit an X chromosome with the XLA gene mutation from her mother, but the X chromosome from the father would ensure that she can still make mature B cells. Although she would not have XLA, she would carry the gene mutation and could pass it on.
A girl could get XLA if she got the gene mutation from both parents. This would be very rare.
A related condition called autosomal agammaglobulinemia also happens because the body can't make mature B cells. The gene mutation that causes this is on a chromosome other than the X or Y chromosomes. Males and females can have this rare condition.
In some cases, a random change in a gene may cause XLA. In this case, it is not passed down by a parent.
Risk factors
The primary risk of XLA is that a mother is a carrier of an XLA-related gene mutation. A risk of XLA may be known in a family, particularly if the mother has brothers or maternal uncles or cousins with the condition.
Families may want to have genetic counseling. This means working with a specialist who can help them understand the benefits and risks of genetic testing. The specialist also helps interpret results.
Complications
With ongoing treatment, people with XLA can live mostly typical lives. They usually can take part in regular activities for their ages.
Even with therapy, repeat infections occur. This requires regular monitoring and prompt treatment.
XLA and repeat infections may lead to long-term complications, including:
- Ongoing lung disease.
- Ongoing inflammation of the sinuses.
- Arthritis.
- Thyroid disease.
- Inflammatory bowel disease.
- Certain cancers.