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X-Linked Agammaglobulinemia

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X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency disease in which the body is unable to produce antibodies needed to defend against pathogens (bacteria, viruses, fungi).

XLA is caused by a mistake in a gene on the X chromosome that encodes Bruton's Tyrosine Kinase (BTK), which is responsible for B-cell development. B-cells produce antibodies that the immune system relies on to fight off infection.

XLA occurs in approximately 1 in 200,000 boys. Mutations in the BTK gene prevent the production of any BTK protein. The absence of that functional protein blocks normal B-cell development and the production of antibodies. Antibodies are the proteins we make to fight infections. Without antibodies, the immune system cannot properly respond to infectious microbes and prevent infection.

The gene associated with this condition is located on the X chromosome. In males (who have only one X chromosome), one altered copy of the gene in each cell is enough to cause the condition. In females (who have two X chromosomes), a mutation in one chromosome does not cause disease. Instead, they may be carriers of the disease.

Female carriers do not have the immune system abnormalities associated with XLA, but they can pass the altered gene to male children, who have a 50 percent chance of having the disease. If a carrier passes the gene to a female child, that child will have a 50 percent chance of being a carrier.

About half of affected individuals do not have a family history of XLA. In most of these cases, the affected child's mother is a carrier of one altered BTK gene. In other cases, when the mother is not a carrier, the affected individual could have a new mutation in the BTK gene.

Rarely, females may have agammaglobulinemia. In these females, BTK is normal but other genes involved in the normal development of B-cells may be affected.

The Primary Immunodeficiency Program at Children’s Medical Center has been recognized as a Center of Excellence by the Jeffrey Modell Foundation for the diagnosis and treatment of patients with primary immunodeficiency including XLA.

Symptoms

Symptoms

Your doctor may suspect XLA if your infant experiences severe and recurrent bacterial infections, including:

  • Ear infections
  • Sinusitis
  • Pneumonia
  • Diarrhea from the parasite Giardia

When babies are first born, maternal antibodies protect them from infection, but this protection only lasts for a period of months.

Infections of the membranes that cover the brain (meningitis) or infections that affect the brain (encephalitis) can occur in children with XLA (and girls with agammaglobulinemia) even when they are being treated with immunoglobulin therapy.

Tests and Diagnosis

Tests and Diagnosis

Your child’s doctor will conduct a physical examination. If your child has XLA, the doctor may notice very small tonsils and lymph nodes.

If your child has these signs, as well as a history of severe bacterial infections, the doctor will order a blood test to evaluate serum immunoglobulins (antibodies). In most children with XLA, all antibody levels are low or absent.

If your child’s doctor suspects XLA, he or she will order a blood test to measure the number of B-cells. A low or absent percentage of B-cells can help establish the diagnosis.

Confirmatory testing will include genetic testing for BTK

Sometimes, radiology studies of the neck, chest, and abdomen or lung function studies may be necessary.

Treatments

Treatments

If your child is diagnosed with XLA, he will be treated with immunoglobulin IgG (antibodies) therapy on a regular basis for the rest of his life. IgG therapy can be given through a catheter in your child’s vein (intravenous; IVIG) or subcutaneously (SCIG). The decision to use one or the other depends on what’s best for your child and your family. There is currently no cure for XLA.

Children with XLA should be followed at the center. If your child develops an infection, antibiotics can treat the infection. Some patients with XLA may have complications including gastrointestinal problems that may require cooperative interaction with gastroenterology specialists.

FAQs

FAQs

What is the prognosis for children diagnosed with XLA?

Most individuals with XLA who receive immunoglobulin on a regular basis can lead normal, healthy lives.

Should my other children be tested for XLA?

If a newborn baby has a brother, sister, maternal cousin or maternal uncle with agammaglobulinemia, the baby is at risk and should immediately be evaluated by an immunologist who will determine what tests will need to be done. These usually include antibody levels in the blood, determination of circulating numbers of B-cells in the blood, and, if a known genetic diagnosis is available, confirmatory testing for both affected and carrier status can be performed.

Where can I find a support group?

We will provide you with resources to help both you and your child. The Resources link on this webpage is also a good source for more information about XLA and support groups.

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