Treatment of WAS
Coping with WAS
Understanding WAS - Introduction and Overview
Wiskott-Aldrich Syndrome (WAS) is a genetically inherited immunodeficiency disease that occurs almost exclusively in males. WAS comprises of a group of serious, but rare disorders, affecting 1 in 250,000 males1. It affects the function of the white blood cells, making these patients susceptible to serious infections. There is also a significant reduction in the size and number of platelets (microthrombocytopenia), causing these patients to bleed easily. WAS is caused by mutations or defects in the WAS protein gene - the WASP gene. Affected patients show a wide variation in the severity of the disease, and four clinical forms2 have been identified:
Classic or Severe WAS
The milder form of WAS or X-Linked Thrombocytopenia (XLT) where the platelets are affected but there is little or no immunodeficiency.
The mildest form called Intermittent Thrombocytopenia where the platelet abnormalities are intermittent and there is no immunodeficiency.
X Linked Neutropenia: Mutations in a specific location of the the WAS gene are also responsible for another clinical entity called X- linked Neutropenia where the platelets are normal but there is a serious defect in the neutrophils (a kind of white blood cell). This disease will not be discussed in this website.
This website mainly addresses Classic WAS, which affects a little over half the total number of patients with WASP mutations3 and XLT, which comprises most of the remainder of the patients. On this website, patients with severe WAS are referred to as Classic WAS, milder forms of the disease are referred to as XLT, and the terms WAS and Wiskott-Aldrich Syndrome are used to refer to both sets of patients. Sometimes the symptoms of WAS and XLT overlap, making the distinction between the two unclear.
Patients with Classic WAS show the following four manifestations of the disease:
- An increased incidence of infections ranging from ear infections and sinusitis to meningitis, sepsis and other serious infections. These infections can be caused by bacteria, viruses, and fungi.
- Prolonged and severe bleeding that can occur spontaneously or with minor injuries due to a microthrombocytopenia. This could be in the form of hematorrhea (bloody diarrhea) during infancy, increased bruising, frequent, severe nose bleeds, and sometimes bleeding in the brain.
- A higher incidence of leukemia, lymphoma, and autoimmune disorders, i.e. conditions in which the body begins to destroy or damage its own red cells, platelets, kidneys etc.
- The skin of these patients is affected by eczema (atopic dermatitis), which may be severe and difficult to treat.
The only proven cure so far for this disease is a bone marrow or cord blood transplant. Successfully transplanted patients go on to lead normal lives, completely free from the disease. For patients with Classic WAS who do not undergo a transplant, the reported life expectancy4 is between 8-14.5 years. With advances in medical care, aggressive management and prevention of infection the life expectancy has increased and there areseveral adult survivors5. It is not uncommon for patients with XLT to reach adulthood, withsome patients surviving into their mid seventies. Several patients have gone on to have families of their own, complete with children and grandchildren (information collected from the WAS Discussion Forum).
Gene therapy has been used in Germany by Dr. Christoph Klein6 on two boys in 2007, and ten boys have been treated so far (verbal communication, Dr. Candotti). Gene therapy is emerging as a potential alternative to cord blood and bone marrow transplant when a suitable match is not available. Experts around the world are collaborating to find the best means of curing this disease as well as how best to advise patients on managing it.
Explore the following sections to better understand WAS.