Wiskott Aldrich syndrome (WAS) is a condition characterized by immunodeficiency and reduced ability to form blood clots. It primarily affects males.
Wiskott–Aldrich syndrome is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet count), immune deficiency, and bloody diarrhea (secondary to the thrombocytopenia). It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrich's original description in 1954.The WAS-related disorders of X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN) may present similar but less severe symptoms and are caused by mutations of the same gene.
People with Wiskott Aldrich syndrome (WAS) have a decrease in the number and size of blood cells involved in clotting (platelets), which is called microthrombocytopenia. This is typically present from birth and can lead to easy bruising or episodes of prolonged bleeding after minor trauma. Eczema, patches of red, irritated skin, is common in affected people. People with WAS also have an increased risk of infections due to dysfunction of many types of immune cells. Some people develop autoimmune disorders, which occur when the immune system mistakenly attacks the body's own tissues and organs. There is also an increased risk of developing some types of cancer, such as lymphoma.
- Easy bruising or bleeding due to a decrease in the number and size of platelets
- Susceptibility to infections, immune disorders and inflammatory disorders
- Increased risk for some cancers (such as lymphoma)
- Eczema is common in affected people
- Abnormality of temperature regulation
- Bruising susceptibility
- Chronic obstructive pulmonary disease
- Otitis media
- Recurrent respiratory infections
WAS is caused by various mutations in the gene coding for the WASp. This mutation is expressed in hematopoietic cells (eg, lymphocytes) and impairs the normal function of WASp in actin polymerization.3 The WASp gene is located on the Xp11.22-23 region of the X chromosome and is inherited in a sex-linked fashion. A male child of a female carrier has a 50% chance of being affected; a female child has a 50% chance of being a carrier.
If the symptoms suggest Wiskott-Aldrich syndrome, a test to measure the immunoglobulin in the blood can help confirm the diagnosis and exclude other immune deficiency disorders. Special tests can measure the body's overall immune system function. A complete blood cell count can reveal if there are low numbers of platelets and if they are the small platelets usually found in Wiskott-Aldrich syndrome. Genetic testing can also determine if the defective gene is present. Other tests may be required depending on the particular symptoms an individual has, such as chest x-ray for possible
The only treatment currently available to cure WAS-related disorders is bone marrow transplant from an allogeneic donor. Allogeneic donors must have human leukocyte antigens (HLA) that match the recipient. Human leukocyte antigens (HLA), which are a form of "histocompatability antigens," are present within the body's tissues and function as an essential part of the immune system. The specific type of HLA within a person's tissues is inherited and is known as the person's "tissue type.". When tissues are transplanted, a donor's and a recipient's HLA tissue types influence the outcome of transplantation. For example, if a donor can be located whose HLA tissue types are very close to those of the recipient, the histocompatability antigens in the donor tissue may not be recognized as foreign and therefore may not be attacked by the recipient's immune system, improving the chances of successful transplantation. Siblings or other blood relatives are the most likely to have HLA types very similar to those of the recipient. Boys with WAS who receive bone marrow transplantation from a matched healthy sibling or closely matched unrelated donor have a greater than 85% chance of being cured if the procedure is performed before five years of age.
Supportive care for WAS-related disorders includes prophylaxis against PCP and appropriate antimicrobial therapy for infections. intravenous immunoglobulin. routine childhood immunizations, and treating eczema with topical steroid therapy. Treatment of significant bleeding sometimes includes platelet transfusions. Splenectomy is no longer recommended as it increases the risk of late death following bone marrow transplantation.
Aspirin and other nonsteroidal anti-inflammatory drugs should be avoided, since these may interfere with platelet function. A protective helmet can protect children from bleeding into the brain which could result from head injuries. For severely low platelet counts, patients may require platelet transfusions or removal of the spleen. For patients with frequent infections, intravenous immunoglobulins (IVIG) can be given to boost the immune system. Anemia from bleeding may require iron supplementation or blood transfusion.
Studies of correcting Wiskott–Aldrich syndrome with gene therapy using a lentivirus have begun. Proof-of-principle for successful hematopoietic stem cell gene therapy has been provided for patients with Wiskott–Aldrich syndrome.
Currently, many investigators continue to develop optimized gene therapy vectors. In July 2013 the Italian San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) reported that three children with Wiskott–Aldrich syndrome showed significant improvement 20–30 months after being treated with a genetically modified lentivirus. In April 2015 results from a follow-up British and French trial where six children with Wiskott–Aldrich syndrome were treated with gene therapy were described as promising. Median follow-up time was 27 months.