The basic defect in X-linked Agammaglobulinemia is a failure of the
B-cell precursors to developing into B-cells and then into plasma cells.
Because of the absence of the cells that make immunoglobulins, these
patients suffer from severe immunoglobulin deficiencies.
Definition of agammaglobulinemia
X-linked Agammaglobulinemia (XLA) was first described in 1952 by Dr.
Ogden Bruton.
This disease sometimes called Bruton's agammaglobulinemia or congenital agammaglobulinemia
was one of the first immune deficiencies identified.
XLA is an inherited immune deficiency.
Affected patients are unable to produce antibodies, the proteins that
make up the gamma globulin or immunoglobulin in blood plasma.
Antibodies role on body’s defense:
Antibodies are an integral part of the body's defense mechanism against
certain micro-organisms (e.g. bacteria, viruses).
They are important to heal infections and to protect the body against
recurrent infections.
Some antibodies are specifically designed to combine with each of the
microorganisms; a bit like a key and a lock.
When microorganisms, such as bacteria, land on a mucous membrane or
enter the body, antibody molecules specific for that microorganism stick to its
surface.
Antibodies stuck to the surface of a micro-organism can have one or more
have one or more beneficial effects for the person.
For example, some microorganisms must attach to cells in the body before
they can cause an infection, and antibodies prevent them from "sticking"
to cells.
Antibodies attached to the surface of some microorganisms also activate
other body defenses that kill bacteria or viruses directly.
e.g., a group of blood proteins called serum complement.
Finally, bacteria coated with antibodies are much easier for phagocytes (white
blood cells) to kill and ingest than bacteria without antibodies.
All of these actions prevent microorganisms from invading the body's
tissues and cause serious infections.
The basic defect in X-linked Agammaglobulinemia is the inability of the
patient to produce antibodies.
Antibodies are proteins that are produced by specialized cells in the body called plasma cells.
Plasma cells develop in an orderly fashion from stem cells in the bone
marrow.
The cells of stem give rise to immature lymphocytes, especially called pro-B
lymphocytes.
The pro-B lymphocytes pro-B lymphocytes develop into pre-B lymphocytes
which, in turn, give rise to B lymphocytes.
Each B-cell carries on its surface a sample of the immunoglobulin that
it is capable of producing.
This immunoglobulin on the surface of the cell can bind foreign
substances, called antigens.
When the B cell comes into contact with its specific antigens, such as pneumococcal
or tetanus toxoid, it develops into an antibody-secreting plasma cell.
Each B cell produces a slightly different antibody (or immunoglobulin)
to enable the body to react to millions of different foreign substances.
Agammaglobulinemia: clinical aspects
Patients with X-linked Agammaglobulinemia (XLA) are predisposed to
infections because of their lack of antibodies.
Infections often occur at or near the surface of mucous membranes, such
as the middle ear, sinuses, and lungs.
But can also, in some cases, reach the bloodstream and internal organs.
As a result, patients with XLA may have infections involving.:
- Sinuses (sinusitis);
- Eyes (conjunctivitis);
- Ears (otitis);
- Nose (rhinitis);
- Lung passages (bronchitis);
- Lungs themselves (pneumonia).
Gastrointestinal infections can also develop, especially infections with
the Giardia parasite.
Giardia can cause abdominal pain, diarrhea, growth problems, or serum
protein loss such as or loss of serum proteins such as gamma globulin.
Some patients with XLA also experience problems with skin infections.
In patients without antibodies, any of these infections can invade the
bloodstream and spread to other organs such as bones, joints, and the brain.
The bacteria that cause the most infections are pneumococcus,
streptococcus, staphylococcus, and Hemophilus influenza.
Specific types of viruses can also cause serious infections in these
patients.
A physical examination shows that most XLA patients have very small tonsils
and lymph nodes (neck glands).
This is because most of the tonsils and lymph nodes are made up of B cells.
Thus, in the absence of B cells,
these tissues are small.
Agammaglobulinemia: Diagnosis
The diagnosis of XLA should be considered in any boy with recurrent or
severe bacterial infections or severe bacterial infections.
Especially, if the patient has small or absent tonsils and lymph nodes…
The first screening test should be an evaluation of serum
immunoglobulin.
In most patients with XLA, all immunoglobulin’s (IgG, IgM, and IgA) are
significantly reduced or absent.
There are exceptions, some patients produce IgM or IgG.
In addition, normal babies produce only small amounts of immunoglobulin
during the first few months of life.
That’s making it difficult to distinguish between a normal baby with an
immunoglobulin production and a baby with a real immune challenge.
If the serum immunoglobulin level is low or the physician suspects a
diagnosis of XLA; B cells number in peripheral blood should be tested.
A low percentage of B cells (almost absent) in the blood is the most
common feature.
It is also the most reliable laboratory finding in laboratory finding in
patients with XLA.
If a male baby has a brother or a cousin or a maternal uncle with XLA,
the newborn is likely to be affected as well.
His family and doctors should immediately determine family and doctors
should immediately determine the percentage of B cells in the cells in the
blood.
So that treatment can be started
before the child becomes sick.
The diagnosis of XLA can be confirmed by demonstrating the absence of
protein in monocytes or platelets.
Also, the diagnosis could be confirmed by detecting q mutation in the BTK
gene.
Almost every family has a different mutation in BTK; members of the same family usually carry the same mutation.
X-Linked Agammaglobulinemia: Inherited
X-linked Agammaglobulinemia (XLA) is a genetic disease that can be
inherited or passed on in a family.
It is important to know the type of inheritance, so that the family can
better understand why a child has been affected.
And be aware of the risk to children in subsequent generations and the
implications for other family members.
Now that the gene responsible for XLA has been precisely identified, it
is possible to test the sisters of an XLA patient.
Also, it is possible to test other relatives, such as the child's
maternal aunts, to determine if they are carriers of the disease.
Women with XLA have no symptoms but have a 50/50 chance of passing the
disease to each of their sons.
In some cases, it is also possible to determine whether
the fetus of a carrier will be born with XLA.
Currently, these genetic tests are performed in only a few laboratories.
Most patients with X-linked Agammaglobulinemia (XLA) who receive regular
immunoglobulin therapy can lead a relatively normal life.
They do not need to be isolated or restrict their activities.
Participation in team sports should be encouraged.
Infections may require extra care from time to time, but children with
XLA can attend school normally and participate in extracurricular activities.
As adults, they are quite capable of having a productive able to have
productive careers and children.
A full and active life should be encouraged and expected.
