Bruton Agammaglobulinemia - Causes, Symptoms, and Treatment

What Is Bruton Agammaglobulinemia?

Bruton agammaglobulinemia is a rare genetic immunodeficiency disorder. It is characterized by the absence of mature B-cells causing the deficiency of antibodies. It was first discovered by Dr. Ogden Bruton in 1952, and therefore it is named Bruton agammaglobulinemia.

Antibodies are proteins (immunoglobulins) produced by immune cells to protect the body against infections like bacteria, viruses, or other harmful bodies. These proteins are immunoglobulin, and there are different types of antibodies like IgM, IgA, IgG, IgD, and IgE. Antibodies are made up of polypeptides composed of two peptides and two amino acids, including two light and heavy chains.

What Are Gammaglobulines?

Gamma globulins are the types of immunoglobulins and function as defense mechanisms for the body to protect against infections and inflammations. The absence of gamma globulin is known as agammaglobulinemia. This increases the risk of getting infected easily.

What Are the Causes of Bruton Agammaglobulinemia?

Bruton agammaglobulinemia is an X- linked genetically inherited disorder. It is caused by the gene mutation in the BTK gene found on the long arm of the chromosome. The BTK gene is a member of the family of nonreceptor protein-tyrosine kinase, which is a signal transduction molecule. Bruton agammaglobulinemia is associated with 544 gene mutations, and these mutations may or may not correlate with the severity of the disorder. There is a 40 percent chance that a person affected with Bruton agammaglobulinemia is by inheritance from the family, and the other 60 percent of people may be affected by the genetic mutation of the gene BTK with no family history.

What Is the Epidemiology of Bruton Agammaglobulinemia?

Following are the factors that state the epidemiology of Bruton agammaglobulinemia -

• Bruton agammaglobulinemia is seen in people with a family history.

• Males are more affected than females. Females are carriers of the disorder without showing any signs and symptoms of the disease.

• It is an inherent genetic disorder and therefore is seen in children between the age group of six to 12 months.

• There is no prevalence of any race.

What Are the Subtypes of Bruton Agammaglobulinemia?

There are three subtypes of Bruton agammaglobulinemia -

• Autosomal recessive agammaglobulinemia.

• X-linked agammaglobulinemia with growth hormone deficiency.

• X-linked agammaglobulinemia.

What Is the Pathology of Bruton Agammaglobulinemia?

Bruton agammaglobulinemia is a rare inherited disorder causing a reduction in the production of B-cells leading to antibody deficiency and increased risk of infections.

BTK is the gene present on the long arm of the chromosome and plays an important role in the production and maturation of B-cells in the body. The gene mutation causes some defects in the gene BTK resulting in the undeveloped production of B-cells in an individual. The absence of immunoglobulin-secreting plasma cells results in the deficiency of immunoglobulins causing hypogammaglobulinemia or agammaglobulinemia.

The deficiency of immunoglobulins causes easy invasion of bacteria, viruses, or other infections in the body. This increases the tendency of bacteria like Streptococcus pneumoniae, Haemophilus influenzae type B, Streptococcus pyogenes, and Pseudomonas to be the main causative agents responsible for infections. It is also observed that some enterovirus can invade and affect the gastrointestinal tract and central nervous system of the body.

What Are the Clinical Features of Bruton Agammaglobulinemia?

Bruton agammaglobulinemia has the following clinical features -

• Patients with Bruton agammaglobulinemia may remain asymptomatic for the first year, as the body may receive some antibodies from the mother during pregnancy. As time passes, the antibodies clear from the baby's body; then, they may start to show some symptoms like recurrent infections and bacterial infections involving the ears, lungs, sinuses, and skin.

• Boys with Bruton agammaglobulinemia have reduced lymphoid or reticuloendothelial organs like tonsils, lymph nodes, spleen, and Peyer patches of the intestine.

• Recurrent respiratory infections.

• Middle ear infections.

• Chronic gastrointestinal problems like vomiting, diarrhea, and nausea.

• Skin-related problems.

• Growth failure.

• Sepsis.

• Kidney inflammation.

• Joint pain.

• Absence of tonsils and adenoids

• Defect in red blood cells.

What Are the Complications of Bruton Agammaglobulinemia?

People with Bruton agammaglobulinemia can handle a normal way of life, although they may experience recurrent infections and other major life-threatening illnesses. Some of the complications are as follows:

• Chronic respiratory disorders.

• Infectious arthritis.

• Increased risk of developing malignancies.

• Damage to the central nervous system.

What Are the Investigations Done for the Diagnosis of Bruton Agammaglobulinemia?

Bruton agammaglobulinemia is a rare genetic disorder. Following are the investigations performed for the diagnosis of Bruton agammaglobulinemia -

• Physical examination and history recording are important to understand the condition.

• Blood investigations are performed to determine the blood cell count.

• Evaluation of serum immunoglobulins.

• A peripheral blood smear helps to determine the cell structure and their activities, and the presence of B-cells.

• Molecular analysis involving single-strand conformation of polymorphism.

• DNA analysis, gel electrophoresis, and reverse transcription polymerase chain reaction are performed for gene BTK.

• Genetic testing is indicated for females who are suspected of having X-linked agammaglobulinemia.

• Testing for CD19 B-cells at the time of birth and determining the elevated T-cell by the process of flow cytometric analysis.

What Are the Treatment Modalities for Bruton Agammaglobulinemia?

Bruton agammaglobulinemia has no cure. However, supportive treatment improves the life of the patient with Bruton agammaglobulinemia.

• Patients must receive lifelong immunoglobulin replacement therapy, either cutaneously or intravenously.

• Antibiotic therapy to reduce bacterial infections.

• Blood transfusion for blood-related problems like anemia and thrombocytopenia.

• Genetic counseling.

• Corticosteroids.

• Avoid live vaccines like measles, mumps, and rubella.

What Is the Prognosis for Bruton Agammaglobulinemia?

Bruton agammaglobulinemia does not have a good prognosis because it is not a curable disorder. An individual with Bruton agammaglobulinemia tends to develop recurrent and chronic lung infections and has an increased risk of malignancies, lymphomas, and adenocarcinoma of the gastrointestinal tract.

Conclusion:

Bruton agammaglobulinemia is a rare X-linked inherited disorder causing failure in the development of B-cells resulting in the deficiency of antibodies. The deficiency of antibodies leads to recurrent and chronic infections. Managing life with Bruton agammaglobulinemia is difficult as it is not a curable disorder. Immunological programs help to overcome the day-to-day problems that arise due to the disorder. It is also recommended to consult an experienced healthcare provider for treatment planning.