The severe combined immune deficiency (severe combined immunodeficiency, SCID) is characterized by a few T cells, or lack thereof, and a low, high or normal number of B cells and natural killer cells. Most infants develop opportunistic infections within the first three months of life. The diagnosis made by detection of a lymphopenia, the absence of or a greatly reduced number of T-cells and by restricted proliferative response of lymphocytes to mitogens. Patients have to be in a protected environment; the definitive treatment consists of hematopoietic Stammzellentranplantation.

(See also Overview of immune deficiency disorders, and approach to the patient with an immunodeficiency disorder.)

The severe combined immune deficiency (severe combined immunodeficiency, SCID) is characterized by a few T cells, or lack thereof, and a low, high or normal number of B cells and natural killer cells. Most infants develop opportunistic infections within the first three months of life. The diagnosis made by detection of a lymphopenia, the absence of or a greatly reduced number of T-cells and by restricted proliferative response of lymphocytes to mitogens. Patients have to be in a protected environment; the definitive treatment consists of hematopoietic Stammzellentranplantation. (See also Overview of immune deficiency disorders, and approach to the patient with an immunodeficiency disorder.) A severe combined immunodeficiency (SCID) is a primary immune deficiency disease include to the combined humoral and cellular immunity deficiencies. This is caused by mutations in one of many different genes causes (eg. As in autosomal recessive forms of Janus kinase 3 [JAK3], protein tyrosine phosphatase, receptor type, C [PTPRC or CD45], recombination activating genes 1 [RAG1] and 2 [RAG2]). Most types are autosomal recessive defects. The gene in question must be mutated on both chromosomes, so that affected a child of SCID. There are 4 different abnormal lymphocyte phenotypes. In all forms of SCID T cells (T-) is missing, according to the type of the SCID, the number of B-cells and / or Natural Killer (NK) cells may be low or absent (B-; NK) or high or normal (B + NK +). But even in normal B-cell count can do this due to lack of T cells that do not work. The natural killer cell function is impaired in general. The X-linked form is the most common. The phenotype is T – B + NK -. Because SCID with the common gamma chain of the IL-2 receptor (a component which consists of at least 6 cytokine receptors) associated serious diseases are the result. It results from a mutation in the IL-2 receptor gamma gene (IL-2RG). The second most common form is the result of adenosine deaminase deficiency (ADA), which leads to apoptosis of B, T and NK-cell precursors; the phenotype is T- B- NK. Another frequently occurring form with a T – B + NK + phenotype resulting from an alpha chain deficiency of IL-7 receptor. Symptoms and signs Most children with SCID suffer before reaching the sixth month of life to candidiasis, persistent viral infections, Pneumocystis jirovecii conjunctivitis and pneumonia and diarrhea, leading to developmental disabilities. For some there is graft-versus-host reactions by maternal lymphocytes or blood transfusions. With other toddlers these diseases between the 6th and 12th month of life occur. There may be an exfoliative dermatitis within the Ommen’s syndrome, a form of SCID. ADA deficiency can lead to bone abnormalities. The thymus is extremely small in all forms, and the lymphoid tissue can be either reduced or completely absent. Without early diagnosis and untreated run all forms of SCID for the kids fatal. Diagnosis Routine newborn screening using the “T-cell receptor excision circle” (TREC) assay history of persistent infection of leukocytes mitogen and vaccine antigen stimulation assays The screening of all newborns using the TREC test is often recommended and is in many US states routinely performed. In infants with a history of persistent infections or other characteristic manifestations of suspected SCID is. A blood count, including the absolute leukocyte count and a differential blood count is analyzed; Immunoglobulin levels are measured. Responses to mitogens and standard vaccine antigens are designed to determine the function of white blood cells and antibodies. The diagnosis of the disease is carried out by: lymphopenia A small number of T cells or no missing lymphocyte proliferation in response to mitogens More tests are performed to determine the type of SCID; they comprise a flow cytometry to determine the number of T-cells, B-cells and natural killer cells. ADA and purine nucleoside phosphorylase levels in leukocytes, erythrocytes and fibroblasts are measured. X-inactivation tests can be performed to determine if the SCID is X-linked inherited. To support the determination of the severity and prognosis test clinicians, patients often common mutations that are characteristic of SCID (eg., IL-2RG, RAG1 and RAG-2, JAK3, Artemis [DCLRE1C]). Genetic testing of family members, with the exception of siblings who were born after diagnosis, not recommended. Therapy reverse isolation Supportive care with immunoglobulin replacement therapy, antibiotics and antifungals Hematopoietic stem cell enzyme replacement for ADA deficiency gene therapy for ADA-deficient SCID patients should be kept in reverse isolation. Treatment with immunoglobulin replacement therapy, antibiotics (including P. jirovecii prophylaxis) and antifungals can help in the prevention of infections, but is not curative. At 90 to 100% of children with SCID or its variants provides a hematoma poetic stem cell transplantation from an HLA-identical sibling with matching Leukozytenmischkultur immunity restored. If an HLA-identical siblings are not available, can haploidentical hematopoietic stem cells of a parent that has been rigorously cleaned of T cells may be used. If the diagnosis before 3 months of age, the survival rate after transplantation of one form or another of hematopoietic stem 96%. Chemotherapy before the transplant is unnecessary because patients can not reject the graft due to lack of T cells. Patients with ADA deficiency who received no bone marrow transplantation, weekly polyethylene glycol-modified bovine ADA can be injected once or twice. The gene therapy was successful in ADA-deficient SCID. After treatment neither leukemia nor lymphomas were registered. Gene therapy has indeed proven to be successful in an X-linked SCID inherited, but was closed early because it has led to T-cell leukemias. The gene therapy for other forms of SCID is still in the development phase. Key points A severe combined immunodeficiency (SCID) is suspected when infants have recurrent infections, graft-versus-host disease or exfoliative dermatitis. The diagnosis is confirmed if the patients have lymphopenia a deficient number of T cells and no lymphocyte proliferative response to mitogens. The number of T-cells, B-cells and natural killer cells is measured to identify the SCID-type. Prophylactic immunoglobulins and antimicrobial agents are administered. A hematopoietic stem cell transplant is performed early, as soon as it is possible. If patients with ADA-deficient SCID not receive bone marrow transplantation, an ADA replacement and sometimes a gene therapy can be used.

Health Life Media Team

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