Pediatric Wiskott-Aldrich Syndrome Workup
- Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD more...
Complete blood counts often support the diagnosis of Wiskott-Aldrich syndrome (WAS). MPV is a routine component of the automated CBC count. Platelets are less than 70,000/mL. The mean platelet volume (MPV) is less than 5 fL. Eosinophilia may be evident.[29, 30]
Always interpret quantitative immunoglobulin levels based on age-related reference range values. Classic Wiskott-Aldrich syndrome is associated with low immunoglobulin M (IgM) and immunoglobulin G (IgG) levels, with normal-to-high immunoglobulin A (IgA) and immunoglobulin E (IgE) levels. However, young infants in particular may not show classic immunoglobulin abnormalities because Wiskott-Aldrich syndrome is associated with attrition in immunologic functions.
Specific antibody defects are most likely in response to polysaccharide antigens. Therefore, isohemagglutinins, IgM directed against the ABO blood group antigens, are typically absent; isohemagglutinins are age-related and are not detectable until infants are older than approximately 6 months. IgG directed against unconjugated pneumococcal antigens are determined postvaccination but are not produced by healthy children younger than 2 years. T-dependent antibody responses to tetanus, diphtheria, and conjugated Hib vaccines vary in Wiskott-Aldrich syndrome. Immune attrition in antibody responses occurs in older patients.
Classic Wiskott-Aldrich syndrome is associated with anergy to delayed-type hypersensitivity (DTH) skin tests. Conventional antigens for DTH testing are tetanus, diphtheria, and Candida; however, immunocompetent infants must have been exposed to the antigen 4-6 weeks prior to testing in order for a positive response to be present. In vitro tests for T-cell function show normal responses in young patients with Wiskott-Aldrich syndrome using nonspecific mitogens such as phytohemagglutinin, concanavalin A, and pokeweed as the stimulus. Defects in T-cell responses are more consistent using allogeneic lymphocytes or periodate as the stimulus. As with humoral responses, Wiskott-Aldrich syndrome is associated with immune attrition of cell-mediated immunity over time.
Autoantibodies may be detected in autoimmune hemolytic anemia (AIHA), immune neutropenia, or immune thrombocytopenia. Such antibodies are the same as those observed in immunocompetent patients.
When a T-cell disorder is suspected, the Immune Deficiency Foundation has a consultative service for physicians. Laboratories in Seattle (the University of Washington), Boston (Children's Hospital), and New York City are funded to provide molecular analysis (Jeffrey Modell Foundation), or they can assist in contacting other research facilities.
Prenatal evaluation of high-risk pregnant women with Wiskott-Aldrich syndrome may be accomplished by karyotyping, gene analysis, and Wiskott-Aldrich syndrome protein detection using cord blood.
Radiography, particularly of the chest, is part of the assessment for new infections.
CT and MRI studies are usually not part of Wiskott-Aldrich syndrome management unless stem cell reconstitution procedures have been performed and posttransplantation complications have developed.
Appropriate cultures and sensitivities are essential to manage acute infections. Blood cultures are especially important in splenectomized patients with Wiskott-Aldrich syndrome, but any patient has increased risk for bacteremia with polysaccharide-coated bacteria.
Monitor renal function and hepatic function at regular intervals.
Workup to determine feasibility for stem cell transplantation requires major histocompatibility (MHC) tests of the patient, parents, and siblings. Screen both the patient and potential donor for infectious agents, including human immunodeficiency virus (HIV), cytomegalovirus (CMV), and hepatitis viruses. Pulmonary, hepatic, and neurologic evaluations of the patient are required to assess chronic organ dysfunction.
Blinded food trials are the criterion standard for determination of food hypersensitivity. However, no adequately studied reports exist of the incidence of food sensitivity or the effect of food restriction on the eczematous dermatitis of Wiskott-Aldrich syndrome. The radioallergosorbent assay test (RAST) for food sensitivity is insensitive, and findings often do not correlate with clinical symptoms.
No procedures are routinely performed.
Older patients with Wiskott-Aldrich syndrome have involution of lymphoid tissues, but depletion of lymphocytes is subtle in younger patients who show only poor development of the follicular areas.
Lymphoid tissues of the gut usually are relatively normal.
The thymus may be small but shows normal architecture, including Hassall corpuscles.
T cells are remarkable for the lack of surface microvilli on which CD43 are expressed in normal lymphocytes.
Specialized techniques can be used to detect poor filopodia formation in platelets and poor F-actin capping at phagocytic vacuoles in phagocytes.
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|Brand(Manufacturer)||Manufacturing Process||pH||Additives (IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors [eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs].)||Parenteral Form and Final Concentrations||IgA Content mcg/mL|
|Kistler-Nitschmann fractionation; pH 4 incubation, nanofiltration||6.4-6.8||6% solution: 10% sucrose, < 20 mg NaCl/g protein||Lyophilized powder 3%, 6%, 9%, 12%||Trace|
|Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization||5.1-6||Sucrose free, contains 5% D-sorbitol||Liquid 5%||< 50|
|Gammagard Liquid 10%
|Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation||4.6-5.1||0.25M glycine||Ready-for-use Liquid 10%||37|
|Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation||4-4.5||Contains no sugar, contains glycine||Liquid 10%||46|
|Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation||4.8-5.1||Contains sorbitol (40 mg/mL); do not administer if fructose intolerant||Ready-for-use solution 5%||< 10|
|Cohn-Oncley fraction II/III; ultrafiltration; pasteurization||6.4-7.2||5% solution: 5% glucose, 0.3% NaCl||Lyophilized powder 5%||< 10|
(Baxter Bioscience for the American Red Cross)
|Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated||6.4-7.2||5% solution: 0.3% albumin, 2.25% glycine, 2% glucose||Lyophilized powder 5%, 10%||< 1.6 (5% solution)|
9/24/10: Withdrawn from market because of unexplained reports of thromboembolic events
|Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization||5.1-6||10% maltose||Liquid 5%||200|
(Swiss Red Cross for the American Red Cross)
|Kistler-Nitschmann fractionation; pH 4, trace pepsin, nanofiltration||6.6||Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl||Lyophilized powder 3%, 6%, 9%, 12%||720|
|Privigen Liquid 10%
|Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration||4.6-5||L-proline (~250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose)||Ready-for-use liquid 10%||≤ 25|