XLA: A Physician’s Perspective
Prior to penicillin, life expectancy was limited for patients with X-linked agammaglobulinemia. Thanks to the advent of intravenous immune globulin, the prognosis today is much more promising.
- By BSTQ Staff
HANS D. OCHS, MD, is a respected researcher whose emphasis has been on the molecular basis of primary immune deficiency diseases (PIDDs) with special interest in the genes linked to Wiskott-Aldrich syndrome, hyper-IgM syndromes, IPEX syndrome, autosomal recessive hyper-IgE syndrome and X-linked agammaglobulinemia (XLA).
Dr. Ochs started the Immunodeficiency Clinic in 1985 at Seattle Children’s Hospital, providing evaluation and care for both pediatric and adult patients with immunodeficiency disorders. He is principal investigator for the U.S. Immune Deficiency Network (USIDnet) and co-founder and member of the summer school faculty devoted to PIDDs. He also is principal editor for the medical textbook Primary Immunodeficiency Diseases: A Molecular and Genetic Approach and co-editor of Immunological Disorders in Infants and Children.
BSTQ: What is XLA?
Dr. Ochs: XLA, which is also referred to as Bruton’s agammaglobulinemia or congenital agammaglobulinemia, was the first immunodeficiency disease ever identified. “X-linked” means that the gene that causes this agammaglobulinemia is located on the X chromosome and therefore primarily affects males, since it is unlikely that females will have two altered copies of the gene.
BSTQ: What are the effects of the disease?
Dr. Ochs: The disease causes the patient to be unable to produce antibodies that make up gammaglobulins in the plasma portion of blood. In XLA, there is a failure of pre-B lymphocytes to mature into B lymphocytes (mature B lymphocytes produce antibodies). Since a patient with XLA produces no antibodies, they are unable to fight off bacterial infections and some viral infections.
BSTQ: What causes XLA?
Dr. Ochs: XLA is caused by inheriting a faulty gene located on the X chromosome. Humans normally have 46 total chromosomes, or 23 pairs in each cell of their body. The 23rd pair determines gender; females have two X chromosomes, and males have one X and one Y chromosome. When females have a disease-causing gene on one of their X chromosomes but do not exhibit any symptoms of the disease, they are referred to as carriers. Males, on the other hand, have only one X chromosome. So if their X chromosome carries a disease-causing gene, then they will exhibit symptoms of the disease. Carrier females have a 50/50 chance with each pregnancy to pass the X chromosome with the faulty gene to a child. If a daughter receives the gene, she will be a healthy carrier like the mother. However, if a son receives the gene, he will have XLA.
BSTQ: Can parents be tested for XLA?
Dr. Ochs: Women can undergo molecular genetic testing of the BTK gene, in addition to prenatal diagnosis (amniocentesis or chorionic villus sampling) for pregnancies when the mother is a known carrier.
BSTQ: How is XLA diagnosed?
Dr. Ochs: Diagnosis is usually made based on a complete medical history and physical examination of the child. In addition, multiple blood tests may be ordered to help confirm the diagnosis.
BSTQ: What’s the long-term outlook for a child with XLA?
Dr. Ochs: Without antibody replacement, these children could die at an early age from severe infections. Children who develop chronic lung disease with bronchiectasis (widening and scarring of the airways) may have a shortened life span in some cases. The good news is, thanks to the availability of immune globulin infusions, children diagnosed and treated early can definitely lead normal, active lives.
