Overview.
DiGeorge syndrome, i.e., congenital absence or hypoplasia of the thymus, is a primary cellular immunodeficiency disorder. It is a primary cellular immunodeficiency disorder in which the thymus and parathyroid glands are absent or underdeveloped due to an embryonic disorder of the third and fourth pharyngeal sacs. Children often have other congenital malformations.
Etiology
The syndrome is polygenic, but deletion of the 22q11 region of chromosome 22 is the main cause.
Symptoms
As a result of fetal hypoparathyroidism and hypocalcemia, newborns present with tetany, and hypocalcemia tends to resolve within 1 year of birth. The child presents with a peculiar face, such as a widened orbital distance, low and cutaneous position of the auricles, a short jaw with a small longitudinal sulcus in the middle of the upper lip, and a cleft nose. Macrovascular anomalies such as tetralogy of Fallot and right-sided aortic arch are often present. If death does not occur in the neonatal period, a variety of severe viral and fungal infections such as Candida and Pneumocystis carinii, and milder bacterial infections, can occur in the first 3 to 4 months of life. Vaccination with live attenuated viral vaccines such as cowpox vaccine and measles vaccine and injection with live bacterial vaccines such as BCG are prone to severe reactions and even death, due to loss of cellular immune function.
Examination
1. Immunological examination
The disease only involves T cells. The cellular immunity function is very poor, the absolute count of peripheral blood lymphocytes is <1.5×109/L, mainly the number of T-cells is significantly reduced, and the rate of E-wreath cell formation is <10%. the T-cell function test is “non-responsive”. The peripheral blood B-cell count is increased, and the serum immunoglobulin concentration is normal.
2. Other auxiliary examinations
X-ray examination showed no thymic shadow.
3. Histopathologic examination
There is a decrease in lymphocytes in the deep cortical thymus-dependent areas of the lymph nodes. The volume of the thymus is small, containing only 10% to 20% of normal thymic tissue, and the parathyroid glands are absent or underdeveloped. The number and distribution of plasma cells in the peripheral lymphoid tissue are normal.
Diagnosis
The disease is diagnosed on the basis of the corresponding clinical manifestations, laboratory and X-ray examinations, and the findings of thymic agenesis, parathyroid and T-cell function abnormalities.
Treatment
1. General therapy
(1) Strengthen nursing care and nutrition in order to improve the patient’s resistance and immunity.
(2) Prevent infection, isolation should be paid attention to minimize the contact with pathogens.
(3) Avoid vaccination For newborns with suspected cellular immunodeficiency, systemic cowpox rash often occurs due to cowpox vaccination, and systemic death due to systemic dissemination of BCG vaccination. Therefore, it should be prohibited to receive live vaccines such as cowpox and lyophilized BCG vaccine, and should also avoid vaccination against measles and polio.
2. Anti-infection therapy
Due to low cellular immunity, the body is unable to kill infected viruses, fungi and other pathogens, therefore, once infection occurs, effective anti-viral agents should be selected for treatment.
3. Immune replacement therapy
Immune replacement therapy is mainly to replenish T-lymphocytes and enhance the function of T-cells.
(1) Transfusion of fresh whole blood The risk of severe GVHR caused by differences in tissue mapping should be considered before blood transfusion.
(2) Transfer factor A lymphokine released by T lymphocytes that transfers normal human-specific immune information to T cells and activates the recipient’s quiescent lymphocytes, thereby restoring and expanding the cellular immune response.
(3) Thymosin is a peptide hormone extracted from bovine or porcine thymus, which not only induces the differentiation and development of T-cells, but also enhances the response of mature T-cells to antigens or other stimuli, improves immune function and regulates immune balance.
(4) Interferon is a lymphokine produced when cells are infected with viruses, which can inhibit the proliferation of viruses and promote the activation of natural killer cells, so it can enhance the antiviral ability of immunocompromised patients.
(5) Interleukin (interleukin-2) is a lymphokine produced by T-helper cells, which promotes the proliferation of lymphocytes and other immunologically active cells and enhances the ability of NK cells and lymphokines to activate killer cells.
(6) Bone Marrow Transplantation Bone marrow transplantation with allogeneic bone marrow to implant normal hematopoietic stem cells can re-establish normal cellular and humoral immune function, which is an ideal treatment for patients with congenital absence or underdevelopment of the thymus.
(7) Thymus transplantation The thymosin secreted by thymic vesicles plays an important role in the maturation of T cells. Therefore, fetal thymus can be implanted into patients in various ways to promote the maturation of T cells and restore cellular immune function.
(8) Immuno-lymphocytes Some cases have been treated with immuno-lymphocytes to obtain a temporary cure.
4. Symptomatic therapy
Calcium gluconate supplementation can control tetany.