X-linked Agammaglobulinemia
What is X-linked agammaglobulinemia?X-linked agammaglobulinemia, also called Bruton's
agammaglobulinemia or congenital agammaglobulinemia, was the first
immunodeficiency disease ever identified. "X-linked" means that the gene
which causes this agammaglobulinemia is located on the X chromosome, and
therefore only affects males. The disease causes the child to be unable to
produce antibodies that make up gamma globulins in the plasma portion of
blood. Antibodies are the body's primary defense against microorganisms
(bacteria, viruses). In X-linked agammaglobulinemia, there is a failure of
pre-B-lymphocytes to mature into B-lymphocytes (mature B-lymphocytes
produce antibodies). As a result, there are no antibodies produced, and
the child's body is unable to fight off bacterial infections and some
viral infections.
Approximately one in 10,000 children are born with this inherited
disease. These boys become very ill since they are prone to develop
infections primarily on the surfaces of mucous membranes, which are found
in the middle ear, sinuses, and lungs. The infections can also involve the
bloodstream or internal organs. With new advances in treatment, most
patients diagnosed and treated early are able to lead relatively normal
lives, without the need for isolation from potential exposure to
microorganisms. In fact, children are encouraged to lead active lives.
What causes X-linked agammaglobulinemia?X-linked agammaglobulinemia is caused by inheriting a gene
which is 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. Females can have a disease-causing gene on one of
their X chromosomes, but not exhibit any symptoms of the disease; they are
referred to as "carriers" for the condition. Males, on the other hand, get
only one X chromosome. So if their X chromosome carries a disease causing
gene, they will have 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
X-linked agammaglobulinemia.
Carrier testing for females in the family is available on a research
basis, in addition to prenatal diagnosis (amniocentesis or chorionic
villus sampling) for pregnancies where the mother is a known carrier.
In some families, an X-linked pattern of inheritance is not present.
This could be because of a small family size, or because, in some cases,
the agammaglobulinemia is the result of a new mutation on the X chromosome
that was not inherited from the mother.
What are the symptoms of X-linked agammaglobulinemia?The symptoms of X-linked agammaglobulinemia usually become
apparent in the first 6 to 9 months of age, but can present as late as 3
to 5 years of age. The following are the most common symptoms of X-linked
agammaglobulinemia. However, each child may experience symptoms
differently. Symptoms may include:
- numerous, serious, and/or life-threatening illnesses, including, but
not limited to the following:
- sinusitis, rhinitis (nasal infection)
- pyoderma (skin infection)
- conjunctivitis (eye infection)
- osteomyelitis (bone infection)
- meningitis (spinal cord infection)
- sepsis (blood stream infection)
- bronchitis (bronchial infection)
- pneumonia (lung infection)
- other infections, including, but not limited to the following:
- gastrointestinal infections (resulting in diarrhea)
- viral infections caused by the hepatitis virus (resulting in
hepatitis), poliomyelitis virus (resulting in polio), and enterovirus
(ECHO virus)
- growth failure
- absence of tonsils and adenoids
- joint disease primarily in the knees, similar to juvenile rheumatoid
arthritis
- autoimmune hemolytic anemia (red blood cell breakdown)
- glomerulonephritis (kidney inflammation)
- neutropenia (decreased neutrophils in the blood)
- dermatomyositis (skin and muscle inflammation)
Cancers, including leukemia, lymphoma, and colon cancer, have been
reported in a small percentage of older patients with X-linked
agammaglobulinemia.
The symptoms of X-linked agammaglobulinemia may resemble other problems
or medical conditions. Always consult your child's physician for a
diagnosis.
How is X-linked agammaglobulinemia diagnosed?A diagnosis of X-linked agammaglobulinemia is usually made
based on a complete medical history and physical examination of your
child. In addition, multiple blood tests may be ordered to help confirm
the diagnosis.
Treatment for X-linked agammaglobulinemia:Specific treatment forX-linked agammaglobulinemia will be
determined by your child's physician based on:
- your child's age, overall health, and medical history
- extent of the disease
- your child's tolerance for specific medications, procedures, or
therapies
- expectations for the course of the disease
- your opinion or preference
Treatment for X-linked agammaglobulinemia may include:
- antibody replacement - through gamma globulin therapy, IVIG
(given intravenously into the bloodstream). This treatment gives
patients the antibodies that they cannot make themselves, in order to
protect against infections and reduce the spread of infections.
- prompt treatment of infections (or giving antibiotics
prophylactically before an infection has occurred).
- avoidance of live viral vaccinations (such as the one given
for measles, mumps, rubella (MMR) and chickenpox (varicella), because
your child could develop the disease for which the vaccine was given.)
Long-term outlook for a child with X-linked
agammaglobulinemia:
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 lifespan, in some cases. However, those children with
X-linked agammaglobulinemia who are diagnosed and treated early
should be able to lead normal, active lives.
More Information
Schneider Children's Hospital Division
of Allergy and Immunology
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