What Is X-Linked Agammaglobulinemia?

X-linked agammaglobulinemia is an X-linked recessive genetic disease, which is a primary immunodeficiency disease caused by a series of developmental disorders of human B cells. The disease is only seen in men, also known as Bruton.

Basic Information

nickname

Congenital hypogammaglobulinemia, Bruton syndrome, Bruton disease

English name

X-linked agammaglobulinemia, XLA

Visiting department

Division of Rheumatology

Multiple groups

boy

Common causes

Bruton tyrosine kinase (BTK) deficiency

Common symptoms

Bronchitis, pneumonia, otitis media, etc.

Causes of X-linked agammaglobulinemia

The disease is due to the defect of Bruton tyrosine kinase (BTK), which hinders the differentiation of primitive B lymphocytes toward B lymphocytes, shortens the lifespan of mature B lymphocytes, and lacks B lymphocytes and plasma cells in peripheral blood, leading to various types of immunity. Insufficient synthesis of globulin, no specific antibody response to many antigens, and immune deficiency in the body. It is prone to repeated bacterial infections.

Clinical manifestations of X-linked agammaglobulinemia

After 4 to 6 months of birth, the protective effect of immunoglobulin G (IgG) from the mother disappears, and severe bacterial infections begin to occur repeatedly, especially upper and lower respiratory tract infections. Bronchitis, pneumonia, and otitis media are common. Meningitis, osteomyelitis, and septic arthritis can also occur. However, it has no special susceptibility to toxins and fungi. The child's lymph nodes were stunted, and the tonsils were small or absent. Despite repeated infections, the lymph nodes and spleen were not enlarged.

Malnutrition and delayed growth are common in children with XLA. The main cause is recurrent infection. It is also prone to allergic, rheumatoid and autoimmune diseases.

X-linked agammaglobulinemia test

(1) Evaluation of routine immune function

1. The total serum immunoglobulin is less than 250mg / dl and IgG is less than 200mg / dl. IgA, IgM, IgD and IgE are difficult to detect.

2. B cells with Ig-like antigens on the surface are significantly reduced in circulation, which is different from common variant immunodeficiency diseases.

3. Lack of the same kind of hemagglutinin or low titer.

4. Very low or absent antibody response to vaccination.

5. Peripheral blood lymphocytes are normal, with the percentage of T cells increasing, while B cells are rare (<0.5%) or absent. T / B cell ratio increased.

6. Cellular immune function is normal.

7. Lymph node and tonsil biopsy revealed a lack of germinal centers and plasma cells (while there are normal amounts of pre-B cells in the bone marrow).

(Two) detection of BTK gene mutations

Genetic analysis confirmed that the pathogenic gene BTK was located on the x chromosome q21.3-22. The BTK gene is 37.5 kb in length and contains 19 exons. Except the first exon, the remaining 18 encode 659 amino acids of the BTK protein. BTK belongs to the Tec family of non-receptor protein tyrosine kinases, and includes 5 different structural segments, starting from the N-terminus, PH, TH, SH3, SH2 and TK segments.

X-linked agammaglobulinemia diagnosis

According to the clinical manifestations of repeated infections, combined with laboratory tests such as serum immunology can make a diagnosis. Establishing a diagnosis depends on BTK genetic testing.

Differential diagnosis of X-linked agammaglobulinemia

1. Infant transient hypogammaglobulinemia

Serum IgG was low, while IgA and IgM were normal. B cell counts in peripheral blood were normal. Lymph node biopsy, although lacking mature plasma cells, has plasma cell-like lymphocytes. Generally, the ability to synthesize immunoglobulin can be restored within 18 months.

2. Normal 5-9 month old infants

Although serum IgG is low, it is higher than 350 mg / dl. IgM and IgA can be detected in serum.

X-linked agammaglobulinemia complications

Repeated injections of human serum immunoglobulin for many years can cause scar formation at the local injection site, with occasional shock-like reactions such as fever, rash, urticaria, asthma and decreased blood pressure.

X-linked gamma globulinemia treatment

1. The principle is to use replacement therapy to supplement antibodies that patients cannot produce.

The method is a periodical intramuscular injection of human serum immunoglobulin. Human normal serum IgG is about 12g / L. Although this scheme can only maintain the patient's serum IgG level at 2g / L, it has obvious therapeutic effects. Repeated injections for many years can cause scar formation at the local injection site, occasional shock-like reactions such as fever, rash, urticaria, asthma, and decreased blood pressure, and should be treated in time as anaphylactic shock.

2. For patients who cannot tolerate pain due to long-term use of intramuscular injection, the following methods can be used instead

(1) Continuous intravenous infusion of plasma to increase serum immunoglobulin levels.

(2) Antihistamines or hydrocortisone can be given monthly before intravenous immunoglobulin infusion, which can significantly reduce the side effects of globulin. Diet therapy was given to those with intestinal malabsorption syndrome.

3. The main methods of diet therapy

Ban wheat food, use a variety of vitamins and proteins, less fat and carbohydrates, avoid slag food, and provide sufficient water. In the early stage of treatment, starchy foods are not used, but more glucose and fructose are given. Can give more protein milk and lactic acid fat-free milk, because it is rich in protein, should be used as the main diet. In addition, proteins such as soy products, chicken protein, lean beef, fish, chicken, liver, and pork tongue can be made into soft and digestible soft foods and gradually increased to maintain nutrition. Note the addition of cod liver oil or vitamin A, D preparations and calcium. Gradually add whole milk, fruit puree, vegetable puree, maltose and sucrose. Finally, starch food is added. You can start with starchy starch products, and then try dry cake powder, rice flour, milk substitute and so on. Be very careful about adding wheat flour.

X-linked agammaglobulinemia prevention

X-linked agammaglobulinemia is a congenital recessive chromosomal genetic disease. Only boys are affected. Consult an expert before pregnancy to screen the sex of offspring with a purpose to avoid the birth of men and achieve the effect of prevention.