Wiskott-Aldrich Syndrome (WAS)

Key Clinical and Laboratory Features

Common clinical features: Abnormal bleeding, petechiae and low platelet counts. Recurrent bacterial sinopulmonary infections, Pneumocystis jirovecii pneumonia, skin infections, and eczema. Some patients with milder mutations in WAShave primarily the platelet and bleeding abnormalities (X-linked thrombocytopenia [XLT]). Some patients with specific mutations in the CDC42 binding domain of WASp have neutropenia but do not have the platelet abnormalities or other aspects of immunodeficiency (X-linked neutropenia).
Other clinical features: Autoimmunity (usually autoimmune hemolytic anemia or thrombocytopenia), malignancy (lymphomas)
Physical exam: Petechiae, easy bruising, eczema
Common laboratory features: Thrombocytopenia with small platelet size (typically greater than 6.0 fL. Note: Some automated counters used in clinical labs disregard the small platelets in WAS as debris and overestimate the platelet size.) IgE is elevated while IgG and IgA are often low. Specific antibody responses typically low. Eosinophilia common. Lymphocyte numbers may be normal or low. T-cell proliferative responses to mitogenic stimulation are often decreased.

	TEST	COMMENTS
GENE	WAS Gene Sequencing	The gold standard for confirming a diagnosis of Wiskott-Aldrich syndrome in a patient with suggestive clinical symptoms. Should be used as the preferred screening test in patients suspected of having X-linked neutropenia (XLN).
PROTEIN	WAS Protein by Flow	Absence of WASp protein in PBMCs is typically associated with a severe Wiskott-Aldrich syndrome phenotype. Decreased (but not absent) protein expression is often associated with a milder, X-linked thrombocytopenia (XLT) phenotype. Approximately 70–80% of patients with a WAS/XLT phenotype have decreased or absent protein expression and can be identified with this test. There are patients with missense mutations in WAS that express a normal amount of non-functional WASp protein. Patients with X-linked neutropenia (XLN) typically have normal WASp protein expression and need to be identified by WAS gene sequencing.
FUNCTION	N/A	There are currently no available clinical tests to evaluate WASp protein function.
OTHER		Complete blood count with differential: Platelet counts low and platelets are small (< 6.0 fL). Eosinophilia is common. Quantitative immunoglobulin levels: IgE is typically elevated. IgG and IgA may be low. Specific antibody titers: Typically low, particularly to pneumococcal and other polysaccharide vaccines. Lymphocyte subset analysis: Lymphopenia may be present. Lymphocyte proliferation to mitogens: Patient T cells often do not proliferate well to mitogens.