About WAS

Understanding WAS

Treatment of WAS

Coping with WAS

  • Diagnosis

    Clinical Diagnosis

    Wiskott-Aldrich Syndrome involves a spectrum of disorders with symptoms ranging from mild to severe.  The diagnosis of WAS should be considered in a male with profound thrombocytopenia (<70,000 platelets/mm3) and small platelet size.  WAS is the only known platelet disorder where the patients have a lower platelet count in conjunction with a smaller platelet size.  There may be a family history of one or more maternally related males with a WAS disorder.

    Additional criteria include recurrent bacterial, viral infections in infancy and early childhood,eczema, the presence of autoimmune disorders, lymphoma, family history of one or more maternal uncles with a WAS related disorder.  Detailed diagnostic criteria are available from The European Society of Immunodeficiencies.

    The diagnosis of XLT1 should be considered in a male with thrombocytopenia with small platelets in the absence of other clinical findings of WAS.  Additional diagnostic criteria include a family history of one or more maternally related males with a WAS disorder.

    Diagnostic Laboratory Testing

    Once the diagnosis of WAS is considered the following laboratory sequence is used.

    1.  Confirm presence of microthrombocytopenia, i.e. platelet count of less than 70,000 associated with a smaller platelet size.  The size of the platelets should be two standard deviations below the normal for the lab.  Many labs are not equipped to measure the size of platelets, especially when they are small and few, and it might be necessary to send the blood sample to another institution to have this done. If the platelets are small, proceed to step 2.

    2.  Assay for intracellular WASp in hematopoietic cells.  Absent or decreased intracellular WASP detection in hematopoietic cells as determined by flow cytometry.  This test is now being used as a screening tool for early diagnosis of WAS followed by a genetic mutation analysis for confirmation and management of the disease.  This testing must be performed at reliable centers that perform the test on a routine basis using standard methods. If WASp is decreased or absent or if suspicion is still high, proceed to step 3.

    3.  Molecular Genetic Testing.  Confirmation of the diagnosis of WAS is done by testing for mutations in the WASP gene on the X chromosome is essential to establishing a final diagnosis.  A combination of the molecular gentic testing along with the WASp levels  may help in estimating the severity of the disease.  However it must be interpreted with caution. Genetic testing is also used for identification of female carriers, for prenatal diagnosis and for preimplantation genetic diagnosis.  Genetic testing detects 98% of mutations in males and 97% of mutations in female carriers.  

    Prognostic Laboratory Testing

    If a patient in whom the diagnosis of WAS has been confirmed, but a decision to transplant has not been made, physicians can run tests on lymphocytes in an attempt to delineate if the patient is likely to have Classic WAS or XLT.  Tests to determine the number and function of the B and T lymphocytes are done.  Tests include the counts of each type of T lymphocyte(absolute counts), and how effectively they function(stimulation tests).  Tests for the B cells include a measurement of the quantity different kinds of Immunoglobulins(Ig)  which are antibodies produced by B lymphocytes ie the IgA, IgG, IgM and IgE.   If the child is over the age of 2 years, the unconjugated pneumococcal polyscaccharide(Pneumovax, PPSV) vaccine can be given and the antibody response to the vaccine is tested.  Individuals with Classic WAS have a greatly decreased production of antibody in response to this vaccine.  Listed below are the patterns seen in a Classic WAS patient.  However, the results on these tests can vary significantly between individuals and can be normal, especially in children.  Interpretation of these tests must be done by a physician who is familiar with WAS. 

    T Lymphocyte

    • Decreased T cell subsets, especially the CD8+T cells.
    • Decreased Natural Killer Cell(NK Cell) function.  Decrease in vitro responses to mitogen , anti-CD3 and antigen stimulation.   

    B Lymphocyte

    • Decreased IgM, increased IgA and increased IgE. 
    • Decreased or absent antibody titers to vaccines such as tetanus, pneumococccus (Prevnar), diphtheria and the unconjugated pneumococcal polysaccharide vaccine(Pneumovax)  
    • Absent isohemagglutinins (these are naturally occurring antibodies that cause reactions if a person is transfused red blood cells of the wrong blood type ie. a person with Type B is given type A etc)   

    Further Reading



    1.  Filipovich, AH, Johnson, J, Zhang, K. WAS-Related Disorders  Gene Reviews www.ncbi.nlm.nih.gov
    2.   Ochs HD, Filipovich AH, Veys P, Cowan MJ, Kapoor N.  Wiskott-Aldrich syndrome: diagnosis, clinical and laboratory manifestations, and treatment.  Biol Blood Marrow Transplant. 2008 Jan;15(1 Suppl):84-90.