Genetic pathologies are rare congenital diseases that are difficult to predict in advance. They occur even at the moment when the formation of the embryo occurs. Most often they are transmitted from parents, but this is not always the case. In some cases, gene disorders occur on their own. Bruton's disease is considered one of these pathologies. It belongs to the primary immunodeficiency states. This disease was discovered recently, in the middle of the 20th century. Therefore, it has not been fully studied by doctors. It is quite rare, only in boys.
Bruton's disease: a history of study
This pathology refers to X-linked chromosomal abnormalities transmitted at the genetic level. Bruton's disease is characterized by impaired humoral immunity. Its main symptom is susceptibility to infectious processes. The first mention of this pathology falls on 1952. At that time, the American scientist Bruton studied the anamnesis of a child who fell ill more than 10 times at the age of 4. Among the infectious processes in this boy were sepsis, pneumonia, meningitis, inflammation of the upper respiratory tract. When examining a childit was found that there are no antibodies to these diseases. In other words, no immune response was observed after infections.
Later, at the end of the 20th century, Bruton's disease was again studied by doctors. In 1993, doctors were able to identify a defective gene that causes immunity disorders.
Causes of Bruton's disease
Agammaglobulinemia (Bruton's disease) is most often hereditary. The defect is considered a recessive trait, so the probability of having a child with a pathology is 25%. The carriers of the mutant gene are women. This is due to the fact that the defect is localized on the X chromosome. However, the disease is transmitted only to the male sex. The main cause of agammaglobulinemia is a defective protein that is part of the gene encoding tyrosine kinase. In addition, Bruton's disease can be idiopathic. This means that the reason for its appearance remains unclear. Among the risk factors that affect the genetic code of the child, there are:
- Alcohol and drug abuse during pregnancy.
- Psycho-emotional overstrain.
- Exposure to ionizing radiation.
- Chemical irritants (harmful production, unfavorable environment).
What is the pathogenesis of the disease?
The mechanism of the development of the disease is associated with a defective protein. Normally, the gene responsible for encoding tyrosine kinase is involved in the formation of B-lymphocytes. They are immune cells that respondfor humoral protection of the body. Due to the failure of tyrosine kinase, B-lymphocytes do not fully mature. As a result, they are not able to produce immunoglobulins - antibodies. The pathogenesis of Bruton's disease is the complete blocking of humoral protection. As a result, when infectious agents enter the body, antibodies to them are not produced. A feature of this disease is that the immune system is able to fight viruses, despite the absence of B-lymphocytes. The nature of the violation of humoral protection depends on the severity of the defect.
Bruton's disease: symptoms of pathology
Pathology first makes itself felt in infancy. Most often, the disease manifests itself by the 3-4th month of life. This is due to the fact that at this age the child's body ceases to protect maternal antibodies. The first signs of pathology may be a painful reaction after vaccination, skin rashes, infections of the upper or lower respiratory tract. Nevertheless, breastfeeding protects the baby from inflammatory processes, since mother's milk contains immunoglobulins.
Bruton's disease manifests itself by about 4 years of age. At this time, the child begins to contact with other children, attends kindergarten. Among infectious lesions, meningo-, strepto- and staphylococcal microflora predominates. As a result, children may be prone to purulent inflammation. The most common diseases include pneumonia, sinusitis, otitis media, sinusitis, meningitis, conjunctivitis. Atuntimely treatment, all these processes can turn into sepsis. Also, a manifestation of Bruton's disease can be dermatological pathologies. Due to a reduced immune response, microorganisms multiply rapidly at the site of wounds and scratches.
In addition, the manifestations of the disease include bronchiectasis - pathological changes in the lungs. Symptoms are shortness of breath, pain in the chest, sometimes hemoptysis. It is also possible the appearance of inflammatory foci in the digestive organs, the genitourinary system, on the mucous membranes. Swelling and soreness in the joints are periodically observed.
Diagnostic criteria for disease
The first diagnostic criterion should include frequent morbidity. Children suffering from Bruton's disease suffer more than 10 infections per year, as well as several times during the month. Diseases can repeat or replace each other (otitis media, tonsillitis, pneumonia). When examining the pharynx, there is no hypertrophy of the tonsils. The same applies to palpation of peripheral lymph nodes. You should also pay attention to the reaction of the baby after vaccination. Significant changes are observed in laboratory tests. In the KLA, there are signs of an inflammatory reaction (increased number of leukocytes, accelerated ESR). At the same time, the number of immune cells is reduced. This is reflected in the leukocyte formula: a small number of lymphocytes and an increased content of neutrophils. An important study is the immunogram. It reflects the decrease or absence of antibodies. This feature allows you to setdiagnosis. If the doctor is in doubt, a genetic test can be done.
Differences between Bruton's disease and similar pathologies
This pathology is differentiated from other primary and secondary immunodeficiencies. Among them are Swiss-type agammaglobulinemia, DiGeorge syndrome, HIV. In contrast to these pathologies, Bruton's disease is characterized by a violation of only humoral immunity. This is manifested by the fact that the body is able to fight viral agents. This factor differs from Swiss-type agammaglobulinemia, in which both humoral and cellular immune responses are impaired. To make a differential diagnosis with DiGeorge syndrome, it is necessary to take a chest x-ray (thymus aplasia) and determine the calcium content. To exclude HIV infection, palpation of the lymph nodes, ELISA is performed.
Agammaglobulinemia treatments
Unfortunately, it is impossible to completely defeat Bruton's disease. Treatment methods for agammaglobulinemia include substitution and symptomatic therapy. The main goal is to achieve a normal level of immunoglobulins in the blood. The amount of antibodies should be close to 3 g/l. For this, gamma globulin is used at the rate of 400 mg/kg of body weight. The concentration of antibodies should be increased during acute infectious diseases, as the body cannot cope with them on its own.
In addition, symptomatic treatment is carried out. Most often prescribedantibacterial drugs "Ceftriaxone", "Penicillin", "Ciprofloxacin". Skin manifestations require topical treatment. It is also recommended to wash the mucous membranes with antiseptic solutions (irrigation of the throat and nose).
Prognosis for Bruton's agammaglobulinemia
Despite lifelong replacement therapy, the prognosis for agammaglobulinemia is good. Continuous treatment and prevention of infectious processes reduce the incidence to a minimum. Patients usually remain able-bodied and active. With the wrong approach to treatment, complications can develop up to sepsis. In case of advanced infections, the prognosis is poor.
Prevention of Bruton's disease
If there is a pathology in relatives or suspicion of it, it is necessary to conduct a genetic examination during the first trimester of pregnancy. Also, preventive measures should include exposure to air, the absence of chronic infections and harmful effects. During pregnancy, stress is contraindicated for the mother. Secondary prevention includes vitamin therapy, the introduction of gamma globulin, a he althy lifestyle. It is also important to avoid contact with infected people.
