Pediatric Westcott-Aldrich syndrome
Introduction
Introduction to Pediatric Wiscott Aldrich Syndrome Wiskott-Aldrich Syndrome (WAS) is an eczema thrombocytopenia with immunodeficiency syndrome, a rare X-linked recessive inheritance affecting both T cells, B cells and platelets. Sexual diseases, with immunodeficiency, eczema and thrombocytopenic triad as clinical manifestations. basic knowledge The proportion of illness: 0.002% Susceptible people: children Mode of infection: non-infectious Complications: hemoptysis, renal insufficiency
Cause
Pediatric Wiscott-Aldrich syndrome etiology
(1) Causes of the disease
The WASP gene is encoded in the OATL1 (DXS6950) and GATA (distal region of DXS1126) regions of Xp11.22, and the binding marker fragments are DXS255 and TIMP, including 12 exons, which are divided into WASP-homologous region 1 (WASP-homology) 1, WH1), pleckstrin homology region (PH), GTPase binding domain (GBD), proline rich region and WASP-homologous region 2 (WH2), WH2 is further divided into verprolin region (VD) and cofilin region (CD), whose expression protein is named Wiskott-Aldrich syndrome protein (WASP).
Most WASP gene mutations are single base changes, leading to missense or nonsense mutations, followed by gene deletions caused by single base deletions or insertions with frameshift mutations, and occasional intron mutations, Chongqing Medical University Children's Hospital A WASP gene point mutation in a pair of male siblings with WAS was recently confirmed and confirmed to be a carrier of abnormal genes.
(two) pathogenesis
WASP is a cytosolic protein expressed only in the hematopoietic cell line, which plays a key role in regulating the reorganization of cytoskeletal structures after lymphocytes and platelets stimulate external stimuli. It has recently been speculated that WASP abnormalities may lead to hematopoietic cell migration. And morphological changes are closely related to the occurrence of WAS.
Missense mutations in the PH region result in decreased WASP levels and mild clinical symptoms; while C-terminal missense and nonsense mutations and intron mutations result in no expression of WASP and severe clinical symptoms; however, this correlation is not absolute, and There are other important genetic and/or environmental factors that control the stability of WASP gene mutations.
Prevention
Pediatric Viscott Aldrich Syndrome Prevention
1. Maternal health care It is known that the occurrence of some immunodeficiency diseases is closely related to embryonic dysplasia. If pregnant women are exposed to radiation, receive certain chemical treatments or have viral infections (especially rubella virus infection), they can damage the fetus. The immune system, especially in the first trimester, can involve multiple systems including the immune system. Therefore, it is important to strengthen maternal health care, especially in early pregnancy. Pregnant women should avoid radiation, use some chemical drugs with caution, and inject rubella vaccine. As far as possible to prevent viral infections, but also to strengthen the nutrition of pregnant women, timely treatment of some chronic diseases.
2. Genetic counseling and family surveys Although most diseases cannot determine the genetic pattern, it is valuable to conduct genetic counseling for diseases in which genetic patterns have been identified, if adults have hereditary immunodeficiency diseases.
Complication
Pediatric Wiscott-Aldrich syndrome complications Complications hemoptysis and renal insufficiency
Can be complicated by hemoptysis, renal insufficiency, organic brain syndrome, mental symptoms, hemianopia, convulsions and hemiplegia, joint swelling and spleen swelling. Involving the posterior pituitary gland causes diabetes insipidus. Eyelid inflammation with ocular protrusion is the most common ocular manifestation of Wegener's granulomatosis. Pathological manifestations include parenchymal tissue necrosis, granuloma, multinucleated giant cells, microabscess and vasculitis, and a few cases eventually developed into malignant lymphoma. Children's cartilage structures are more susceptible to damage. The incidence of nasal deformity in children is twice that of adults, and subglottic stenosis is five times that of adults.
Symptom
Pediatric Wiscott-Aldrich Syndrome Symptoms Common symptoms Thrombocytopenic bleeding tendency Septic lymph node enlargement Black stool repeated infection of granulocytes to reduce meningitis hemoptysis
1. Bleeding tendency bleeding often occurs within 6 months after birth, even at birth, including purpura, melena, hemoptysis and hematuria, thrombocytopenia, platelet volume is reduced to the characteristics of the disease, glucocorticoids and high dose IVIG It is not possible to increase the number of platelets. In some cases, thrombocytopenia and bleeding tendency are the only clinical manifestations, called X-linked thrombocytopenia (XLT).
2. Atopic eczema is seen in 80% of children with WAS. It often occurs after birth and can be mild or severe. Bacterial infections and food allergies can aggravate eczema.
3. The incidence of infection with suppurative otitis externa is 78%, sinusitis is 24%, pneumonia is 45%, serious infection such as sepsis is 24%, meningitis is 7%, intestinal infection is 13%, and patients can develop serious viral infection. For example, cytomegalovirus, varicella virus, herpes simplex virus, etc., the incidence of Pneumocystis carinii and Candida infection are 9% and 10%, respectively, and thrombocytopenia, repeated infection, eczema triad only accounted for 27% The only manifestation of 5% of cases before diagnosis was thrombocytopenia.
4. Other performance
(1) The incidence of autoimmune diseases is 40%, the most common is hemolytic anemia, followed by vasculitis, kidney disease, allergic purpura and inflammatory bowel disease, other neutropenia, dermatomyositis , recurrent neurovascular edema, iritis and cerebrovascular disease.
(2) Tumors occurred in 13% of cases, the average age was 9.5 years old, and the incidence was higher with age, mainly lymphatic malignant tumors, gliomas, acoustic neuromas and testicular cancer.
(3) The liver, spleen and lymph nodes are swollen.
Examine
Pediatric Wiscott-Aldrich syndrome check
Serum IgM concentration decreased, IgG concentration was only slightly reduced or normal, while IgA and IgE may increase, immunoglobulin and albumin catabolism rate is twice that of normal people, homologous hemagglutinin titer is very low, for polysaccharide antigen , diphtheria, tetanus toxoid or influenza bacillus b vaccine antibody response is low, phage x174 intravenous injection can not stimulate immune memory response and immunoglobulin isotype conversion, in general, the immune response to live attenuated virus vaccine is normal, Some of the sick children have IgG subclass defects, mainly IgG2 deficiency, the number of B cells increased significantly, and the number of T cells decreased significantly.
About 50% of children have a low proliferative response to lymphocytes, and 90% of children have a delayed skin allergic reaction (less application due to local bleeding).
The decrease or disappearance of lymphocyte CD43 glycoprotein expression is also a significant marker of the disease. The microvilli on the surface of lymphocytes is less or absent. Scanning electron microscopy shows that the surface of lymphocytes in children is smoother than normal.
Thrombocytopenia and platelet volume are also characteristic of this disease, platelet count is (1 ~ 4) × 10 10 / L, bone marrow megakaryocytes are normal or increased, suggesting that platelet production is ineffective, due to persistent blood loss can cause iron deficiency anemia.
1. X-ray examination of chest radiographs often showed pulmonary infection, occasionally subperiosteal hemorrhage, the lateral side of the skull can be seen in the posterior pharyngeal lymphatic tissue dysplasia.
2. B-ultrasound can be found in the liver, splenomegaly, joint fluid and so on.
3. CT examination should be done by CT and other examinations, and intracranial hemorrhage can be found.
Diagnosis
Diagnostic identification of children's Wiscott-Aldrich syndrome
The diagnostic criteria are: repeated infections in male infants, eczema, thrombocytopenia, hemorrhagic rash accompanied by increased serum IgA and IgE, decreased IgM, lack of homologous hemagglutinin, decreased antibody response to polysaccharide protein, and particularly reduced platelet volume. In the diagnosis of children with WAS, the reduction of T cell CD43 expression is also diagnostic.
For atypical cases, gene sequence analysis can be clearly diagnosed, genetic diagnosis is also used for prenatal diagnosis and clear carrier of male infants, and fetal blood samples can be used for prenatal diagnosis by analyzing the number and size of platelets.
When thrombocytopenia and hemorrhage are the only manifestations, they should be differentiated from thrombocytopenic purpura, and the gene sequence analysis can confirm the diagnosis.
