In a separate group, SCID is distinguished in combination with other large defects (well-identified SCID)

Wiskott-Aldrich syndrome (1:250,000). X-linked immunodeficiency.

Cause: mutation of the WASP gene encoding the synthesis of the protein of the cytoskeleton of lymphocytes and platelets, which leads to a defect in intercellular interactions and cell activation. The synthesis of antibodies to polysaccharide antigens is impaired. Thrombocytopenia is associated with reduced platelet size and increased platelet destruction.

Age of manifestation : the first weeks, months of life.

Gender: Boys get sick.

Key clinical and laboratory features:

1. Hemorrhagic syndrome

2. Eczema (atopic dermatitis)

3. Severe infections: bacterial – otitis, sinusitis, pneumonia, diarrhea, viral – herpes, CMV.

4. Hypoplasia of the thymus, splenomegaly

5. Thrombocytopenia <70*10 12 /l , decrease in platelet size

6. Lymphopenia (decreased CD3 + , CD4 + )

7. Decreased IgM, increased IgA, IgE.

The disease often manifests with hemocolitis or hemorrhagic manifestations (bleeding from the umbilical wound, petechiae and ecchymosis, epistaxis, hematuria). Later, eczema, bacterial, fungal or viral infections join. The average life expectancy is about 3 years. Children die from bleeding, infections, tumors. 40% develop autoimmune diseases. In patients older than 8 years, the frequency of neoplasias (lymphomas, leukemias) is increased.

Treatment: antibacterial, antifungal, antiviral , administration of intravenous immunoglobulins . With severe hemorrhagic manifestations, splenectomy is performed. The use of live vaccines is contraindicated. The radical method of treatment is TCM or hematopoietic cell transfusion.

Prognosis: without bone marrow transplantation, ½ of patients die from bleeding and tumors, ½ from severe infections. With TCM up to 5 years, the prognosis is relatively favorable.

Syndrome of ataxia-telangiectasia (Louis-Bar) (1:1000 – 1:1000 000). Autosomal recessive disease.

Cause: mutation of the ATM gene, which regulates DNA repair, leading to chromosomal translocations on chromosomes 7 and 14 at the T-cell receptor (TCR) and Ig loci. Neurological disorders are based on a neurodegenerative process associated with impaired DNA repair, damage to the cerebellum, and disappearance of Purkinje cells.

Age of manifestation : first 1-3 years of life, sex : both.

Key clinical and laboratory features:

1. Neurological disorders (cerebellar ataxia, decreased tendon reflexes, divergent strabismus, loss of motor function)

2. Sinopulmonary infections (bronchitis, pneumonia with the development of bronchiectasis, pulmonary fibrosis)

3. Conjunctival or facial telangiectasias

4. Hypoplasia of the thymus, lymph nodes, tonsils

5. Increase in α-fetoprotein (AFP)

6. Lymphopenia, decrease in the number of CD3 + , CD4 + , CD8 +

7. Decreased IgA and in some cases IgG

Cerebellar ataxia – a clinical marker of the disease, occurs already at the beginning of the 2nd year of life. The child begins to walk, unsteadiness of gait is noted, often falls. At school age, tendon reflexes decrease, atrophy of the muscles of the spine and lower extremities progresses. Ataxia progresses slowly, but adult patients cannot do without a wheelchair. Telangiectasias appear later, between 3-6 years, localized on the conjunctiva, in the area of the eyes, knees, elbows. A characteristic feature is repeated infections of the respiratory tract with the development of chronic pneumonia, bronchiectasis, and pulmonary fibrosis. With age, the risk of developing tumors increases, in childhood lymphomas predominate, in adults – solid tumors.

Treatment: syndromic therapy with antibiotics, intravenous immunoglobulins, physiotherapy to maintain muscle tone, chemotherapy in the event of lymphoproliferative diseases. Limitation of X-ray exposure!

The prognosis is poor, the average life expectancy is 20 years. The most common causes of death: respiratory failure due to chronic pneumonia, malignant neoplasms.

2. Predominantly cellular (lymphoid) immunity defects. It makes up 5-10% of all immunodeficiencies. It is manifested by a violation of the proliferation and differentiation of T-lymphocytes. The primary violation of the cellular link of immunity in most cases is accompanied by a secondary violation of the synthesis of antibodies. In this regard, the clinical manifestations of T-cell immunodeficiencies may resemble those of SCID.

DiGeorge syndrome (1:3000-1:6000). Autosomal recessive disease.

Reason: spontaneous deletion in the region of the long arm of chromosome 22 leads to a malformation of the 3rd and 4th gill arches, which is realized by hypo- and aplasia of the thymus, parathyroid glands, congenital heart defects, anomalies of the facial skeleton. Immunodeficiency is associated with the absence or hypoplasia of the thymus and narrowing of the springboard for the maturation of T-lymphocytes.

Age of manifestation : in the first year of life, gender : both.

Key clinical and laboratory features:

1. Dysplastic facial features (abnormal auricles, hypertelorism, wide bridge of the nose, fish mouth, malformations of the palate)

2. Severe forms of ARI (parainfluenza, adenovirus, MS)

3. Hypocalcemic seizures

4. Delayed physical and psychomotor development, mental retardation

5. Defects of the heart and blood vessels (tetralogy of Fallot, dextroposition of the aorta)

6. Reducing the number of CD3 + to 1500-500 cells / μl

7. Hypocalcemia, decreased parathyroid hormone levels.

In most children, the disease is diagnosed in the first months of life, when they are examined for heart disease. Less commonly, the disease manifests as persistent viral or fungal infections or begins with hypocalcemic seizures. With a decrease in T-lymphocytes less than 500 cells / μl, the risk of systemic fungal infections, pneumocystis pneumonia increases, the clinical picture resembles SCID. If the patient survives 6 months of age, there is a gradual recovery of T-cell immunity.

Treatment: for infectious complications, antibacterial, antifungal, antiviral therapy is indicated . Ca and vitamin D preparations are recommended to correct parathyroid function deficiency. For severe T-cell deficiency, fetal thymus transplantation (thymus less than 14 weeks of gestation) can be used.

Reasons for transplant failure: The recipient’s T-cells remember the HLA molecules of the fetal thymus as “their own” and do not interact well with antigen-presenting cells in the periphery.

Forecast: mortality in the first 6 months is 85%. With full forms of DiGeorge syndrome, the prognosis is unfavorable, patients die at an early age from heart defects or infections. With partial forms of DiGeorge syndrome, the prognosis is relatively favorable, T-cell deficiency is compensated with age.

Autoimmune polyendocrinopathy syndrome (mucocutaneous candidiasis) (1:9000-1:25000). Autosomal recessive.

Cause: Mutation of the AIRE-1 (autoimmune regulator) gene on the long arm of chromosome 21. The AIRE-1 gene is of fundamental importance for the development of autoimmune diseases. Its mutation leads to a violation of the expression of organ-specific autoantigens in the thymus during the formation of T-lymphocytes with a violation of autoregulation and the development of autoimmune diseases. The cause of immune disorders is not fully known. Patients have a selective T-cell deficiency against fungi of the genus candida.

Age of manifestation : in the first year of life, gender : both.

Key clinical and laboratory features:

1. Mucocutaneous candidiasis, onychomycosis

2. Repeated bacterial infections of the respiratory tract, skin, ENT organs

3. Ectodermal dysplasia (total caries, alopecia)

4. Endocrinopathy (hypoparathyroidism, adrenal insufficiency, hypogonadism)

5. Vitiligo, alopecia

6. Autoimmune hepatitis

In the immune status, mosaic unexpressed deviations, an increase in the level of immunoglobulins.

Treatment: diet low in sugars, oral hygiene, systemic and topical antifungals, prolonged antibiotic therapy, immunosuppressive therapy for the treatment of autoimmune hepatitis, replacement therapy for the correction of endocrine disorders. Radical therapy does not exist.

Prognosis: average life expectancy up to 20 years, the severity of the condition is determined by bacterial infections, endocrinopathies, autoimmune disorders.

Be First to Comment

Leave a Reply

Your email address will not be published.