Wiskott-Aldrich Syndrome (WAS)
- Inheritance: X-linked recessive
- Gene: WAS
- Protein: WASp
- Tests: WAS Gene Sequencing, WAS Protein by Flow
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.
|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.|