Wiskott-Aldrich Syndrome Workup

Updated: Oct 16, 2019
  • Author: Peter N Huynh, MD; Chief Editor: Michael A Kaliner, MD  more...
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Laboratory Studies

Obtain a complete blood cell count with manual differential, lymphocyte and plately enumeration, and peripheral blood smear. The most consistent finding at diagnosis is thrombocytopenia and small platelets. Lymphopenia is also characteristic for classic WAS during childhood.

Screen for WASp mutations with flow cytometery with anti-WASp antibody.

Patients with mutated WASp expression may be missed with flow cytometery, therefore direct Sanger sequencing of patient DNA is essential for confirming the diagnosis in patients with abnormal protein expression.

Measure quantitative serum immunoglobulin levels of all other classes (ie, immunoglobulin A [IgA], immunoglobulin G [IgG], immunoglobulin E [IgE]).

In classic WAS, IgM levels are low and IgG levels are relatively normal, but IgA and IgE levels may be elevated.

Test humoral immune function by measuring the patient's ability to develop antibody responses to standard polysaccharide and protein antigen vaccines (eg, pneumococcal vaccine, tetanus toxoid), using preimmunization and postimmunization antibody titers.

Measure cellular immune function by examining lymphocyte proliferative responses to mitogens, alloantigen, and recall antigens and the patient's ability to react to anergy battery skin testing with delayed-type (type IV) hypersensitivity responses. The latter skin test antigens typically consist of candidal, mumps, trichophyton, and tetanus toxoid antigens.

In WAS, defects in a patient's response to polysaccharide vaccination and anergy are common. Responses to protein antigens and lymphocyte proliferation may also be impaired. [2]

Enumeration of T- and B-cell subsets by flow cytometry may be helpful.

This test provides quantitative and morphologic information about cellular elements of the immune system and information about platelet numbers and morphology. T-cell deficiency may occur, although B-cell number is usually preserved (albeit with possibly significantly altered phenotypic expression). Thrombocytopenia and small platelets are present in patients with this disorder. [2, 41] Patients with WAS may have unstable sialoglycoprotein CD43 (sialophorin) on the surface of lymphocytes [10] . One study of 154 patients with WAS revealed lymphopenia in 22% and low CD8+ T-cell counts in 61%. [2]

Consider genetic testing for carrier status. Prenatal diagnosis via amniocentesis or chorionic villus sampling is possible. [42]

Patients may require other tests based on clinical presentation. Serious disorders (eg, bleeding, infection, malignancy) form part of this syndrome.


Imaging Studies

If pneumonia is considered, obtain a chest radiograph.

Use computed tomography to evaluate for splenomegaly, help rule out malignancy, help rule out intracranial bleeding, evaluate sinus infection, and/or evaluate for pulmonary infections.



Consider obtaining a bone marrow biopsy to assist diagnosis in complex cases or to evaluate for hematologic malignancy. However, patients generally do not require bone marrow biopsy. If performed, megakaryocytes usually appear normal. [41]

If meningitis is considered, a lumbar puncture may be necessary.

Recurrent otitis media may require tympanostomy tube placement.


Histologic Findings

Platelets in patients with WAS are small, with a decreased diameter and volume. One study of platelets in patients with WAS found an average diameter of 1.82 micrometer (normal = 2.23 micrometer) [43] , and another study found a mean volume of 3.8-5 fL, compared with 7.1-10.5 fL in individuals without WAS. [41]