Understanding 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:

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.


Epidemiology and Disease Mechanism

The WAS Gene and its Mutations





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1 Perry GS 3rd, Spector BD, Schuman LM, Mandel JS, Anderson VE, McHugh RB, Hanson MR, Fahlstrom SM, Krivit W, Kersey JH.   The Wiskott-Aldrich syndrome in the United States and Canada (1892-1979).  J Pediatr. 1980 Jul;97(1):72-8.2 Notarangelo, Luigi D; Miao, Carol H; Ochs, Hans D,  Wiskott-Aldrich Syndrome.   Curr Opin Hematol. 2008 Jan;15(1):30-6.3 Jin Y, Mazza C, Christie JR, Giliani S, Fiorini M, Mella P, Gandellini F, Stewart DM, Zhu Q, Nelson DL, Notarangelo LD, Ochs HD.  Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation.  Blood. 2004 Dec 15;104(13):4010-9.4  Dupuis-Girod S, Medioni J, Haddad E, Quartier P, Cavazzana-Calvo M, Le Deist F, de Saint Basile G, Delaunay J, Schwarz K, Casanova JL, Blanche S, Fischer A.  Autoimmunity in Wiskott-Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients.   Pediatrics. 2003 May;111(5 Pt 1):e622-7.5 Imai K, Morio T, Zhu Y, Jin Y, Itoh S, Kajiwara M, Yata J, Mizutani S, Ochs HD, Nonoyama S.  Clinical course of patients with WASP gene mutations.   Blood. 2004 Jan 15;103(2):456-64.   6 Boztug, K, Dewey, RA, Diez, IA, Manfred, S, Kerstin, S, Jana, D, Sonja, N, Klaus, K, Irina, K, Lazlo, M, von Kalle, C, Welte, K, Klein, C.  Hematopoietic Stem Cell gene Therapy for Wiskott Aldrich Syndrome. American Society of Hematology Conference, December 10, 2007.