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December 29, 2016 00:08

Wiskott-Aldrich Syndrome |Symptoms and Treatment of Wiskott-Aldrich syndrome

syndrome Wiskott-Aldrich (Wiscott-Aldrich syndrome, WAS) (OMIM # 301000) - X-linked disease, the main symptoms of which are mikrotrombotsitopeniya, eczema and immune deficiency.The incidence of the disease is about 1 in 250,000 male births.

history of the disease

Wiskott in 1937 first described three brothers with the manifestations of thrombocytopenia, melena, eczema, and frequent infections.B1 954 year Aldrich suggested X-linked mode of inheritance of the disease on the basis of descriptions of several male patients from the same family.In 1994, parallel to the two laboratories (Derry, Kwan) was mapped gene whose mutations lead to disease.Despite the fact that to date have been described more than 200 families with Wiskott-Aldrich syndrome, the pathogenetic mechanisms of the disease has not been fully deciphered.

Pathogenesis syndrome Wiskott-Aldrich

Currently WAS is a disease with a lesion of a single gene was mapped by positional cloning and called WASP (Wiskott-Aldrich Syndrome Protein).The

gene is located on Hr11.23 and consists of 12 exons.

protein WASP eksprecciruetsya exclusively in cells of hematopoietic.The function it is not fully known, it is assumed that the WASP is mediating the activation of cellular signals and the subsequent reorganization of the cellular skeleton.

WASP gene mutations include the entire spectrum: missense, nonsense, deletions, insertions, splicing mutation sites, and large deletions.Distribution of the mutations along the length gene unevenly, although mutations were found in all 12 exons of the gene.Some mutations are located in the "hot spots" (S290T, G257A, G431A) - these mutations are found in multiple families.

Thrombocytopenia occurs in all patients with Wiskott-Aldrich syndrome: the platelet count typically less than 50,000 / microliter, and platelet volume decreased to 3,8-5,0 tl.Available studies suggest that thrombocytopenia with Wiskott-Aldrich syndrome is primarily associated with increased platelet destruction.

Symptoms of the syndrome Wiskott-Aldrich

severity of disease manifestations in patients with Wiskott-Aldrich syndrome varies from intermittent thrombocytopenia with minimal hemorrhagic manifestations to severe illness with severe infectious and autoimmune syndromes.Thus, so far it failed to establish a clear correlation between the severity of the disease and the type of mutation.Discrepancies between several groups of researchers can be explained by the lack of clear classification of Wiskott-Aldrich syndrome, and as a result, the researchers classified patients with a similar severity of illness in different ways.Tem not less, in general, the majority of missense mutations in exon 2 are accompanied by a mild course of disease, and the CDS nonsense mutation leads to a severe syndrome Wiskott-Aldrich.

Symptoms of the syndrome Wiskott-Aldrich syndrome Classification

Wiskott-Aldrich

At the moment, there is no uniform classification of Wiskott-Aldrich syndrome.The most commonly used is the scoring system described in the review Ochs 1998. This system is based on the assumption that all patients mikrotrombotsitopeniya WAS is present, and that most, if not all patients develop an immunodeficiency of varying severity.The lack of a history of eczema, or mild, treatable and eczema lungs, frequent infections are not going without complications, fits easily flow Wiskott-Aldrich syndrome (1-2 points).Severe eczema, recurrent infections are not treatable, autoimmune diseases and malignancies characteristic of the so-called classical syndrome Wiskott-Aldrich, which is estimated at 3-4 points (Medium heavy) and 5 points (heavy).

syndrome Wiskott-Aldrich Diagnostics

As for Wiskott-Aldrich syndrome is characterized by a wide spectrum of clinical manifestations, this diagnosis should be considered in all boys with bleeding, congenital or early diagnosed thrombocytopenia.Infections and immunological disorders may not be available or, conversely, to be pronounced.Some patients may develop autoimmunity.

According diagnostic consensus adopted ESID (the European Society for Immunodeficiencies) absolute criterion setting WAS diagnosis is to identify the significant reduction of WASP protein concentration in the blood cells and / or identification of the gene mutation.

syndrome Wiskott-Aldrich Diagnostics

Treatment of Wiskott-Aldrich syndrome

first choice attraction WAS is a hematopoietic stem cell transplantation (HSCT).Survival of patients after WAS TRNC from HLA-identical siblings is 80%.Transplantation of HLA-identical unrelated donors is most effective in children under the age of 5 years.Unlike HSCT from an HLA-identical donor, the results of HSCT from partially compatible (haploidentical) donor related were not as impressive, although many angora describe 50-60% survival rate, which is quite acceptable, given the poor prognosis of the disease is of HSCT.

Splenectomy reduces the chance of bleeding, but it is accompanied by an increased risk of septicemia.Splenectomy increases the number of circulating platelets and an increase in their size.

syndrome Treatment of Wiskott-Aldrich