The diagnosis can be made on the basis of clinical findings, the peripheral blood smear, and low immunoglobulin levels. Typically, IgM levels are low, IgA levels are elevated, and IgE levels may be elevated; paraproteins are occasionally observed. Skin immunologic testing (allergy testing) may reveal hyposensitivity. Individuals with<unk>  however are at higher risk for severe food allergies. Not all patients have a positive family history of the disorder; new mutations do occur. Often, leukemia may be suspected on the basis of low platelets and infections, and bone marrow biopsy may be performed. Decreased levels of WASp are typically observed. The current gold standard for diagnosis is DNA sequence analysis, which can detect WAS and the related disorders XLT and XLN in 95% of patients and carriers. + Diagnostic criteria for<unk>  Mandatory criteria * Low platelets, known as thrombocytopenia (<70,000 platelets/mm3) on two separate tests, AND * Small platelets (platelet volume <7.5 fL) Definitive * Pathogenic WAS variant (or deletion) detected on genetic testing, OR * Absent or reduced WAS expression via Northern blot analysis of lymphocytes from a fresh blood sample, OR * Absent or reduced WAS protein in lymphocytes, OR * Maternal family history of<unk>  or a WAS-related disorder (X-linked thrombocytopenia or X-linked congenital neutropenia) Probable * Eczema, OR * Recurrent infections (either viral or bacterial), OR * Autoimmune diseases (including hemolytic anemia, vasculitis, arthritis, inflammatory bowel disease, and IgA nephropathy), OR * Cancer (lymphoma, leukemia, or brain tumor), OR * Abnormal antibody response to polysaccharide antigens and/or low isohemagglutinins (antibodies against foreign blood cells responsible for ABO incompatibility) Possible * Same as above, but had spleen removal (a treatment for thrombocytopenia) so may no longer meet mandatory criteria, OR * Mandatory criteria only Classification Jin et al. (2004) employ a numerical grading of severity: This score, which ranges from 0 to 5, may have clinical utility for predicting disease severity. Those with higher WAS scores (e.g., 5) at younger ages (e.g., age less than 5 years old), are thought to be at highest risk for increased morbidity and mortality related to their condition. As individuals can develop more WAS-related symptoms (e.g. autoimmune disease, malignancy) with age, one's WAS score can increase over time. A lower WAS score may be more compatible with conservative management versus higher WAS scores that may favor intervention with treatments such as hematopoietic stem cell transplant. +WAS clinical score Score Definition Clinical<unk>  0 Neutropenia (low white blood cell count) or myelodysplasia only X-linked neutropenia (XLN) 0.5 Intermittent thrombocytopenia (low platelet counts sometimes but not always) X-linked thrombocytopenia (XLT) 1 Thrombocytopenia and small platelets (microthrombocytopenia) XLT 2 Microthrombocytopenia plus normally responsive eczema or occasional upper respiratory tract infections XLT 2.5 Microthrombocytopenia plus therapy-responsive but severe eczema or airway infections requiring antibiotics XLT/Wiskott–Aldrich<unk>  (WAS) 3 Microthrombocytopenia plus both eczema and airway infections requiring antibiotics WAS 4 Microthrombocytopenia plus eczema continuously requiring therapy and/or severe or life-threatening infections WAS 5 Microthrombocytopenia plus autoimmune disease or malignancy XLT/WAS + autoimmune disease or cancer
Wiskott–Aldrich syndrome
Common variable immunodeficiency
Chronic granulomatous disease
Severe combined immunodeficiency
SAPHO syndrome
Hyper-IgM syndrome type 5
Ataxia–telangiectasia
Hyper-IgM syndrome type 2