synonymWAS syndrome(WAS syndrome) generally refers to eczema, thrombocytopenia and immunodeficiency syndrome
Eczema thrombocytopenia with immune deficiency syndrome, also known as Wiskott Aldrich syndrome (WAS), is a rare X-linked recessive genetic disease. With eczema, thrombocytopenia and immune deficiency as clinical manifestations, it is prone to autoimmune diseases and malignant tumors.The incidence of newborn WAS is (1~10)/million, mostly male.The main treatment is stem cell transplantation to reconstruct immune function.
On May 11, 2018, the National Health Commission and other five departments jointly formulated the First Batch of Rare Diseases Catalogue, which included eczema, thrombocytopenia and immunodeficiency syndrome.[1]
TCM disease name
Eczema thrombocytopenia with immune deficiency syndrome
Foreign name
WAS
alias
Wiskott Aldrich syndrome
Multiple population
Most of them are male.
common symptom
Eczema, thrombocytopenia and immune deficiency are the clinical manifestations.
Hereditary or not
yes
Science popularization in China
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The certification expert of this term is
Song Hongmei|Chief physician
Department of Pediatrics, Union Medical College Hospitalto examine
Eczema thrombocytopenia with immune deficiency syndrome
Foreign name
WAS
Alias
Wiskott Aldrich syndrome
Multiple population
Most of them are male.
common symptom
Eczema, thrombocytopenia and immune deficiency are the clinical manifestations.
Hereditary or not
yes
pathogeny
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The disease originates from the mutation of WAS gene encoding WAS protein (WASp) and is an X-linked recessive genetic disease.WASp is only expressed in the hematopoietic system and plays an important role in the differentiation and migration of hematopoietic cells, cell signal transduction, immune synapse formation and lymphocyte apoptosis, which can lead to a variety of abnormal immune cell functions.There are more than 300 mutations in WAS gene, leading to different defects in WASp, which leads to a variety of clinical phenotypes.
clinical manifestation
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1. More common in boys.
2. Bleeding tendency: It is the most important clinical feature of WAS. The patient has bleeding tendency after birth, which can be manifested as ecchymosis, purpura, epistaxis, gingival bleeding, hematuria, bloody stool, hematemesis, subconjunctival bleeding, intracranial hemorrhage, etc.
3. Eczema: It is another characteristic manifestation of WAS, which often occurs in a few months after birth.With age, eczema can become serious and difficult to control.Eczema is typically distributed on the head, face, forearm and popliteal fossa, but can spread all over the body as the disease progresses.Some eczema is accompanied by bleeding or infection.
4. Repeated infection: most patients will suffer from repeated infection, especially pneumonia, otitis media, meningitis, upper respiratory tract infection and skin infection.
5. Others: hepatosplenomegaly is common.Some children have arthritis, autoimmune hemolytic anemia, kidney disease, etc.Older children are prone to malignant diseases, especially malignant tumors of the lymphatic reticular system.
6. The atypical children have no recurrent infection and eczema.
inspect
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1. Physical examination
Most children have bleeding tendency and eczema. Physical examination can find physical signs such as ecchymosis and purpura. Observation of the characteristics of eczema is helpful for diagnosis.
2. Laboratory inspection
(1) Blood routine
Platelet count in blood routine examination is an indicator for clear diagnosis. It can be seen that the number of platelets decreases significantly and the size of platelets decreases.
(2) Determination of serum immunoglobulin (Ig)
Most of the children had normal serum IgG levels, decreased IgM, and increased IgA and IgE.Homologous lectins are often not detected.The Ig level of a few children is normal.
(3) Cellular immunity
With the increase of age, more patients have lymphopenia and the number of T cells decreases.The proliferation and differentiation of T cells were reduced.
(4) WASp expression
Analyzing the expression of WASp in the cytoplasm of peripheral blood mononuclear cells by commercial antibodies and flow cytometry is a rapid diagnostic method, which can confirm WAS within a few hours.
(5) Gene testing
Polymerase chain reaction (PCR) combined with sequencing method can accurately detect the mutation site and type of WAS gene in children, and make a clear diagnosis.However, in some patients with gene mutation in intron region or regulatory region, the gene screening can be normal.
diagnosis
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According to eczema, thrombocytopenia, repeated infection triad with thrombocytopenia, typical WAS can be initially diagnosed.WASp deficiency or decreased expression level, and WAS gene detection (PCR sequencing, etc.) can assist in diagnosis.
Diagnostic criteria: There is no domestic diagnostic criteria for this disease, and the international diagnostic criteria published by the Pan American Immunodeficiency Group and the European Society for Immunodeficiency in 1999 are generally followed.
(1) Determine diagnosis
Male, with fewer congenital platelets (<70 × 10/L) and small platelet volume, has at least one of the following: ① WAS gene mutation. ②The deletion of WAS mRNA in lymphocytes was confirmed by RNA imprinting. ③Lymphocytes do not express WASp. ④Maternal cousins have fewer platelets and smaller platelet volumes.
(2) Possible diagnosis
Male, with fewer congenital platelets (<70 × 10/L) and small platelet volume, has at least one of the following: ① eczema ②The antibody response to polysaccharide antigen is abnormal. ③Repeated bacterial or viral infection. ④Lymphoma, leukemia or brain tumor.
(3) Suspected diagnosis
Male patients with less congenital platelets (<70 × 10/L) and small platelet volume, or male patients with thrombocytopenia undergoing splenectomy, have at least one of the following: ① eczema ②The antibody response to polysaccharide antigen is abnormal. ③Repeated bacterial or viral infection. ④Autoimmune disease. ⑤Lymphoma, leukemia or brain tumor.
complication
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Due to thrombocytopenia and immune deficiency, it can cause infection, hemorrhage, malignant tumor and other complications.
treatment
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Individualized comprehensive treatment plan should be formulated according to the severity, course of disease, mutation of WAS gene and expression of WASp.
1. General treatment
Support treatment and antibiotic prevention and treatment are necessary, such as the use of compound sulfamethoxazole to prevent pneumocystis pneumonia.If necessary, intravenous infusion of gamma globulin, platelet transfusion and splenectomy can be performed.Severe eczema can be treated with glucocorticoid.
2. Hematopoietic stem cell transplantation
Hematopoietic stem cell transplantation is the most effective method to cure WAS.Hematopoietic stem cell transplantation should be performed as early as possible after the diagnosis of WAS children without WASp expression.
3. Gene therapy
Because gene therapy avoids rejection after transplantation, it does not need matching, which is conducive to timely treatment of WAS.However, due to the risk of inserting mutations to activate proto oncogenes, the safety of its treatment needs to be further improved, and it is still in the experimental stage.
prognosis
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The overall prognosis is poor. If hematopoietic stem cell transplantation is not carried out, the patient will eventually die of complications such as infection, hemorrhage and malignant tumor.Hematopoietic stem cell transplantation and other treatments can improve the prognosis.
prevention
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The fundamental prevention method is to carry out prenatal diagnosis for high-risk infants of WAS to avoid birth of defective infants.Prenatal diagnosis methods include amniotic fluid cell analysis based on DNA sequencing and umbilical cord blood WASP flow detection.
nursing
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1. The child should avoid strenuous exercise, prevent collision and trauma, and closely observe the skin condition of the child for bleeding spots, ecchymosis, and ecchymosis.
2. Pay attention to food hygiene and avoid allergens.
3. Try to avoid going to densely populated public places to reduce the incidence of infection.
