Bruton-Gitlin syndrome is an immunodeficiency that deprives the B cells of the immune system of the ability to produce and secrete antibodies and can therefore be classified as an antibody deficiency syndrome. The disease, which is usually mild, is inherited in an X-linked recessive manner and is based on a defect in the BTK gene. Infusions with antibodies or stem cell transplants are considered for symptomatic treatment.
What is Bruton-Gitlin syndrome?
B lymphocytes are immunologic cells from the lymphocyte cell group. They form the basis for the specific humoral immune system in humans and are capable of producing antibodies after contact with a specific antigenic stimulus. Thus, they fulfill important tasks in the adaptive immune response, of which they form the basis. Bruton-Gitlin syndrome is a hereditary disease that deprives B cells of the ability to produce and secrete antibodies. Thus, the syndrome is a form of immunodeficiency and is associated with a congenital disorder of the body’s immune system. The disorder was named after its first describers, Ogden Carr Bruton and David Gitlin. In various literature, instead of Bruton-Gitlin syndrome, it is also referred to as Bruton’s disease, Bruton’s syndrome, Bruton-type agammaglobulinemia, or congenital hypogammaglobulinemia. Among immunodeficiencies, Bruton’s disease constitutes a rather mild form associated with a comparatively favorable prognosis. Because Bruton-Gitlin syndrome is associated with antibody deficiency, it is sometimes included among the antibody deficiency syndromes.
Causes
Bruton-Gitlin syndrome has its cause in the genes. The disorder is passed on in an X-linked recessive manner. Because of its linkage to the male chromosome, immunodeficiency manifests primarily in male newborns. Females, unlike male individuals, possess multiple X chromosomes. If one of their X chromosomes is defective, the healthy chromosome can compensate for the defective chromosome. In males, compensation of this kind is inconceivable because they have only a single X chromosome available. If this chromosome is defective in the sense of the syndrome, this automatically leads to the onset of the disease. Women, on the other hand, can be silent carriers of Bruton-Gitlin syndrome without ever suffering from symptoms. In the case of Bruton-Gitlin syndrome, the immunological defect affects tyrosine kinase, which plays a crucial role in the growth of immunological B cells. Due to the disease, stagnation in B cell maturation occurs. The maturation arrest of pre-B cells results in the inability to produce and secrete antibodies in a physiologically planned manner. The primary cause of the inherited disease is a receptor called Bruton tyrosine kinase (BTK), which is encoded by the BTK gene on X chromosome.
Symptoms, complaints, and signs
Bruton-Gitlin syndrome is a rather mild form of immunodeficiency. The first symptoms of the syndrome characteristically manifest in the second to third month of life. At this stage of life, the antibodies transferred from the mother are gradually replaced in a healthy infant’s body with the body’s own gamma globulins. In most cases, the early symptoms of the disease are recurrent skin infections. Respiratory tract infections may also be symptomatic. The increased susceptibility of affected individuals to infections is most often manifested in infections with bacteria such as staphylococci, Haemophilus influenzae, or streptococci. The defense reaction in contact with viruses, protozoa, fungi and Mycobacterium tuberculosis may be maintained in individual cases. Basically, patients with Bruton-Gitlin syndrome have a demonstrable antibody deficiency in all organs of the body as well as in the blood. Women with the syndrome, unlike men, usually show no symptoms of the disease until the end of their lives.
Diagnosis and course
In cases of recurrent infections, the physician usually orders a differential blood count. This blood count can guide the diagnosis to Bruton-Gitlin syndrome. Electrophoretic examination of the gamma globulin fraction may strengthen the suspected diagnosis of the syndrome. Molecular genetic diagnosis confirming genetic damage on the X chromosome is considered diagnostic. Compared to other immunodeficiencies, the prognosis for patients with Bruton-Gitlin syndrome is favorable. The syndrome is characterized by mild progression and rarely requires measures such as bone marrow transplantation.
When should you go to the doctor?
Bruton-Gitlin syndrome must be treated by a doctor in any case. There is usually no self-healing in the process. If diagnosed early, further complications can be avoided. The doctor should be consulted if the child suffers very frequently from infections or inflammations. In this case, the children suffer mainly from skin complaints or flu. The symptoms can be very different in boys and girls. Even in adulthood, the symptoms of this disease can occur. In this case, a doctor should also be consulted if the patient suffers from a significantly weakened immune system and falls ill more often with infections. Diagnosis and treatment of this disease can be performed in most cases by a pediatrician or by a general practitioner. As a rule, however, those affected are dependent on lifelong treatment. However, with the help of antibodies and stem cell transplants, the symptoms of Bruton-Gitlin syndrome can be relatively well limited and alleviated.
Complications
Bruton-Gitlin syndrome can result in a variety of complications that depend greatly on the severity of the syndrome. However, most patients suffer from an immunodeficiency and cannot produce sufficient antibodies. Due to the lack of antibodies, many affected individuals develop infections and inflammations on the skin. Patients are also more likely to have harmless infections and suffer from a lowered immune response. Bruton-Gitlin syndrome is much milder in women than in men. Women show almost no symptoms in this disease. Bruton-Gitlin syndrome leads to limitations in the patient’s life because the immune system is weakened. The disease is considered incurable, which is why treatment can only limit the symptoms. Antibodies are administered to the patient in the form of infusions. The affected person is dependent on these infusions for the rest of his or her life. Life expectancy is not reduced with proper treatment, and there are no further complications. If the infusions have no effect, a stem cell transplant is necessary. Deficiencies of the immune system can be compensated. Complications occur only in the form of infections and inflammations, from which the affected persons are more often ill.
Treatment and therapy
Bruton-Gitlin syndrome is considered an incurable disease to date. Causative therapies are not available to patients because the causative genetic defects of the X chromosome are not revisable. Although the disease is currently incurable, some symptomatic treatment approaches are available to patients. Patients can be given a solution of the missing antibodies via a subcutaneous or intravenous infusion. Antibody infusions of this type can compensate for the body’s lack of antibody production capacity, at least partially improving the humoral immune response. In more severe cases, stem cell transplantation may become necessary. This involves the transfer of stem cells from a donor organism to a recipient organism. Allogeneic stem cell transplantation refers to hematopoietic, or blood-forming, stem cells. The first allogeneic stem cell transplants were performed in 1968 on several patients with inherited immunodeficiency diseases. Since then, stem cell transplantation has been an established option for immunocompromised patients to compensate for more severe immunodeficiencies.
Prospect and prognosis
Because Bruton-Gitlin syndrome is a hereditary disorder, it can only be limited symptomatically. For this reason, genetic counseling is always advisable for parents if there is a further desire to have children. Patients are dependent on regular infusions with antibodies to alleviate the symptoms of the disease. As a rule, lifelong therapy is necessary, since there is no causal treatment of the syndrome. Stem cell transplantation is performed only in severe cases in which infusions fail to alleviate the symptoms. However, even this does not completely cure Bruton-Gitlin syndrome, so that patients continue to be dependent on infusions and regular examinations.If Bruton-Gitlin syndrome remains untreated, the patient’s life expectancy is usually significantly reduced due to the weakened immune system. The affected persons are thus restricted in their everyday life and have to protect themselves against various diseases. Especially elderly people can be severely affected by Bruton-Gitlin syndrome. Often, the syndrome also leads to psychological complaints, so psychological treatment may also be necessary.
Prevention
Because Bruton-Gitlin syndrome is a genetic disorder, prevention options are limited. Exogenous factors do not appear to be involved in the development of the disease. Thus, genetic counseling in family planning is considered the only promising preventive measure to date. In the context of the disease, genetic counseling also plays a role for women who do not show any symptoms. As silent carriers of the defect, they may be able to pass the disease on to their offspring. Whether the decision is made against having children of one’s own is up to each individual.
Follow-up
The options for follow-up care are relatively limited in Bruton-Gitlin syndrome. It is a congenital disorder that cannot be treated causally, but only symptomatically. A complete cure can therefore also not be achieved, so that the affected person is dependent on lifelong therapy and treatment to alleviate the symptoms. The antibodies are administered to the affected person by infusion into the blood. The infusions should always be performed regularly to avoid further complications and discomfort. Likewise, the affected person should not expose himself to any particular dangers or pathogens in order not to unnecessarily burden the body’s immune system. In severe cases, transplantation of stem cells is also necessary to keep the affected person alive. In some cases, the patient’s life expectancy may also be significantly reduced by Bruton-Gitlin syndrome. Not infrequently, the disease also leads to psychological complaints or depressive moods, which can occur not only in the patient, but also in the relatives and friends and acquaintances. At this, a visit to a psychologist is usually necessary, although contact with other sufferers of Bruton-Gitlin syndrome can also have a positive effect on the course of the disease.
What you can do yourself
Since Bruton-Gitlin syndrome is an inherited genetic defect of the X chromosome, there are no therapies that could cure this disease. A self-healing is therefore impossible. The symptoms that occur can only be alleviated. Early diagnosis of Bruton-Gitlin can prevent health complications. Typically, the first symptoms appear in two- to three-month-old male infants. At this time, the antibodies transferred from the mother during pregnancy are replaced with the baby’s own gamma globulins. The missing antibodies are supplied to the patient by means of infusions. This creates a temporary improvement in the immune system. In particularly severe cases of the disease, stem cell transplantation is performed. In this case, hematopoietic stem cells are transferred. The life expectancy of patients is reduced due to the weakened immune system if Bruton-Gitlin syndrome is not treated. Preventive genetic counseling assists in family planning. This includes both women and men. Although women often do not show symptoms of Bruton-Gitlin, they can pass the genetic defect on to their own children. The counseling here clarifies the risks of inheritance and thus helps to decide for or against having one’s own children.