Agammaglobulinemia in children

Agammaglobulinemia in children is a typical disease with an isolated deficit of antibody production. Genetic defects lead to disruption of the early stages of maturation of B lymphocytes, and as a consequence, repeated bacterial infections from the first years of life, expressed hypogammaglobulinemia and a sharp decrease or absence of B-lymphocytes in peripheral circulation.

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How does agammaglobulinemia develop in children?

In most patients with agammaglobulinemia (about 85%), a mutation of the Btk gene (Bruton's tyrosine kinase), located on the X chromosome, is revealed . The disease is called X-linked (or Bruton) agammaglobulinemia (XLA). Half of patients with this defect have no family history, mutations are spontaneous in nature. 5% of patients with agammaglobulinemia have a mutation of the heavy alpha chain gene. In a small number of patients, defects in other components of the pre-B cell receptor (surrogate light chain, mu heavy chain), as well as signaling protein BLNK, are noted. All these defects have autosomal recessive inheritance. The absence of one of the above proteins leads to a violation of the signal transmission from the pre-B-cell receptor, and as a consequence, to the lymphocyte maturation block.

Symptoms of agammaglobulinemia in children

Clinical symptoms of agammaglobulinemia practically do not differ depending on the molecular genetic defect

An important sign of a defect in B lymphocytes in a patient is the hypotrophy of the tonsils and lymph nodes. Lymphonoduses basically consist of follicles, which, in turn, are mainly represented in B lymphocytes. In the absence of B cells, follicles are not formed and lymph nodes are very small.

In most patients, infections will debut in the first year of life, after the catabolism of maternal antibodies. However, about 10% of patients are diagnosed at the age of more than 4 years. Perhaps in this group there is a higher residual concentration of immunoglobulins.

The vast majority of patients with agammaglobulinemia develop repeated or chronic infections caused by encapsulated bacteria, especially S. Pneumoniae and H. Influenzae, such as pneumonia, otitis, sinusitis, conjunctivitis, enterocolitis. Somewhat less severe infections occur: meningitis, osteomyelitis, destructive pleuropneumonia, sepsis, septic arthritis, pyoderma and suppurative infections of the subcutaneous tissue.

In addition to H. Influenzae, S. Pneumoniae, patients with agammaglobulinemia are highly susceptible to infections caused by mycoplasmas and ureoplasms. Mikollasmas and ureoplasms are the cause of the development of chronic pneumonia, purulent arthritis, cystitis and subcutaneous tissue infections. With zgammaglobulinemia, lambliasis is often detected. Patients with humoral defects are highly susceptible to enterovirus infections: ECHO and Coxsackie. The cause of the infection may be a vaccine strain of poliomyelitis. Enteroviruses cause both severe acute and chronic encephalitis and encephalomyelitis. Manifestations of engerovirus infections can be dermatomyositis-like syndrome, ataxia, headaches, behavioral disorders.

Of non-infectious symptoms, patients have ulcerative colitis, scleroderm-like syndrome, and, paradoxically, symptoms of seasonal and drug allergies.

In patients with agammaglobulinemia, neutropenia often develops, which can be complicated by characteristic infections (S. Aureus, P. Aerogenosa).

Diagnosis of agammaglobulinemia

The diagnosis criterion is a decrease in the serum IgG concentration of less than 2 g / L in the absence of IgA, IgM and circulating B-lymphocytes. Some patients with XLA have an "attenuated" phenotype in which trace amounts of IgG and IgM can be detected, and the number of B lymphocytes in the peripheral blood is up to 0.5% of all lymphocytes. Usually, such patients have a later debut of the disease.

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Treatment of agammaglobulinemia

The basis for the treatment of agammaglobulinemia is substitution therapy with intravenous immunoglobulin. At the beginning of treatment and with the development of severe infections, the immunoglobulin is administered in a dose of 0.2-0.3 g / kg of body weight 1 time every 5-7 days for 4-6 weeks. This mode of administration of an immunoglobulin allows the normal concentration of IgG in the serum to be achieved. Regular maintenance therapy is performed once every 3-4 weeks at a dose of 0.4 g / kg. The pretreatment level of IgG should be at least 4 g / l. In the case of enteroiuretic infection, high-dose therapy with intravenous immunoglobulin (2 g / kg) is indicated 1 time for 5-7 days for 4 weeks.

In the presence of chronic foci of infection (usually in the lungs), patients are indicated the appointment of a continuous prophylactic antibacterial therapy (sulphometoxazole-trimethoprim in the form of monotherapy or a combination with fluoroquinolones or amoxiclav).

In the case of persistent neutropenia, accompanied by clinical manifestations, growth factors are used. Stem cell transplantation with agammaglobulinemia is not indicated.

What prognosis does agammaglobulinemia have in children?

The use of combined therapy of agammaglobulinemia with the use of regular immunoglobulin and antibiotics significantly improved the prognosis of the disease. An early initiated adequate replacement therapy with intravenous immunoglobulin avoids the formation of chronic infections, and significantly reduces the number of episodes of acute infections and the incidence of other complications. Recently, most patients receiving adequate treatment reach adulthood.