Pediatric Wiskott-Aldrich Syndrome
Wiskott-Aldrich syndrome (see the image below) is an X-linked recessive immunodeficiency disorder characterized in one third of patients by the triad of recurrent bacterial sinopulmonary infections, eczema (atopiclike dermatitis), and a bleeding diathesis caused by thrombocytopenia and platelet dysfunction. 
The characteristic triad of bleeding, eczema, and recurrent infections in Wiskott-Aldrich syndrome generally become evident during the first year of life, with petechiae and ecchymoses of the skin and oral mucosa and bloody diarrhea being the first clinical signs. Although only one third of patients with WASP (Wiskott-Aldrich syndrome protein) mutations express the classic triad at presentation, other manifestations include the following:
Thrombocytopenia (almost 90%) 
Only hematologic abnormalities (20%) 
Only infectious manifestations (5%) 
Only eczema (0%) 
Autoimmune phenomena 
See Clinical Presentation for more detail.
Examination for Wiskott-Aldrich disease includes evaluation for/of the following:
Signs of bleeding, infection, malignancy, and atopy
General appearance and vital signs
Height and weight growth parameters
Head and neck assessment
Laboratory studies used in the evaluation of Wiskott-Aldrich syndrome include the following:
CBC count: Often supports the diagnosis
Quantitative serum immunoglobulin levels
Functional testing of the humoral and cellular components of the immune system
Delayed-type hypersensitivity skin tests
Other tests that may be appropriate, depending on the clinical situation, include the following:
Cultures (eg, blood) and sensitivities
Renal function tests
Hepatic function tests
Major histocompatibility tests of the patient, parents, and siblings to determine feasibility for stem cell transplantation
Screening of patient and potential donor for infectious agents (eg, HIV, CMV, hepatitis viruses)
Radiography, particularly of the chest, is part of the assessment for new infections. However, CT and MRI studies are not usually utilized for Wiskott-Aldrich syndrome unless stem cell reconstitution procedures have been performed and posttransplantation complications have developed.
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.
See Workup for more detail.
Wiskott-Aldrich syndrome has a variable disease severity, depending on the genotype.  Accordingly, treatment strategies range from conservative to early definitive intervention, including antibiotics, antivirals, antifungals, chemotherapeutic agents, immunoglobulins, and corticosteroids. Agents are selected based on the patient’s clinical presentation and response.
Medications used in the treatment of Wiskott-Aldrich disease include the following:
Antibiotics (eg, amoxicillin, amoxicillin/clavulanate, cefuroxime, ceftriaxone, vancomycin, nafcillin)
Inhaled bronchodilators (eg, albuterol, salmeterol, beclomethasone, fluticasone)
Hyperimmune globulins (eg, varicella-zoster immune globulin)
Immunizations (eg, vaccines, including diphtheria and tetanus toxoids [DT or Td], acellular pertussis, conjugated HIB, conjugated pneumococcal vaccine, unconjugated meningococcal A and C, hepatitis B [HBV], influenza)
Corticosteroids (eg, prednisone, methylprednisolone, fluocinolone)
Immunoglobulins (eg, immune globulin)
Surgical intervention may be necessary for complications of bleeding, such as the following:
Neurosurgery if subdural hematoma forms
Surgical evacuation of hematomas
Surgical intervention to halt blood loss after any minor trauma
Splenectomy as an option in cases of coexisting severe thrombocytopenia and frequent bleeding when stem cell reconstitution is not considered
Supportive care in patients with Wiskott-Aldrich syndrome includes the following:
Transfusions of platelets and/or red blood cells
Bone marrow transplantation
Infusions of intravenous immunoglobulin G
Wiskott-Aldrich syndrome (WAS) was first described by Wiskott in 1937 and was further characterized by Aldrich in 1954. It is a rare X-linked recessive immunodeficiency disorder characterized by the triad of recurrent bacterial sinopulmonary infections, eczema (atopiclike dermatitis), and a bleeding diathesis caused by thrombocytopenia and platelet dysfunction.  However, only a third of patients with the syndrome have the classic triad.  Almost 90% of patients have manifestations of thrombocytopenia at presentation, 20% have only hematologic abnormalities, 5% have only infectious manifestations, and none have only eczema.  WAS platelets are usually smaller than those of idiopathic thrombocytopenia, but a macrothrombocytopenia has been described in WAS.  Other symptoms may include autoimmune phenomena and malignancies. 
An infant with WAS is seen in the image below.
Wiskott-Aldrich syndrome occurs in males but can occur in females when the X chromosome that contains the functional allele is inactivated, although this is rare. There may be multiple revertant genotypes in patients with Wiskott-Aldrich syndrome. 
The gene for the Wiskott-Aldrich syndrome protein (WASp) is localized to Xp11.22-23 and consists of 12 exons that encode a 502 amino acid (53 kD) protein. WASp is a cytosolic protein expressed on all hematopoietic cell lineages and is essential for normal antibody function, T-cell responses, and platelet production.  It also regulates actin polymerization, transcription, and a selective, post-transcriptional role in Th2 effector function.  About 300 mutations have been found throughout the gene and can include base pair substitutions, insertions, and deletions. These mutations can result in different clinical phenotypes, including classic Wiskott-Aldrich syndrome, X-linked thrombocytopenia, intermittent thrombocytopenia, and neutropenia. [11, 12]
The type of specific mutation, its location within the gene, and its effect on protein expression appear to determine an individual patient’s clinical phenotype. 
WASP is a key regulator of actin polymerization in hematopoietic cells. As a cytoskeletal regulator, it is necessary for induction of normal immunity. WASp functions as a bridge between signaling and movement of the actin filaments in the cytoskeleton. WASp has several well-defined domains (pleckstrin, cofilin, verprolin, SH3) that are involved in signaling, cell locomotion, and immune synapse formation.
In vitro studies with T cells, platelets, phagocytes, and dendritic cells of patients with Wiskott-Aldrich syndrome reveal defects in the formation of microvilli, filopodia, phagocytic vacuoles, and podosomes, respectively; these structures depend on cytoskeletal reorganization of actin filaments. Researchers also identified many different mutations that interfere with the protein binding to Cdc42 and Rac GTPases, among other binding partners, most of which are involved in regulation of the actin cytoskeleton of lymphocytes. [14, 15] The actin cytoskeleton is responsible for cellular functions, such as growth, endocytosis, exocytosis, and cytokinesis.
Mutations of WASP are located throughout the gene and either inhibit or dysregulate normal WASp function. WASp facilitates the nuclear translocation of nuclear factor kappa-B (NF-kB) and was shown to play an important role in lymphoid development and in the maturation and function of myeloid monocytic cells. In mice, WASp was found to be essential for NF-ATp activation, and for nuclear translocation of p-Erk, Elk1 phosphorylation, and c-fos gene expression in T cells. These defects in mutated forms of WASP are the likely etiology of defective IL-2 expression and T-cell proliferation in Wiskott-Aldrich syndrome. Low T cell numbers resembling T-B+ SCID has been described in WAS. 
Clot formation is interrupted by impaired formation of fibrin strands. WASp binds to calcium and integrin binding protein (CIB) on platelets. The complex of CIB and mutated WASp reduces alpha2-beta3 integrin mediated cell adhesion and causes defective platelet aggregation, resulting in bleeding.
Research has shown phenotype-genotype correlation. Classic Wiskott-Aldrich syndrome, X-linked thrombocytopenia, and X-linked neutropenia occurs when WASp is absent, when mutated WASp is expressed, and when missense mutations occur in the Cdc42-binding site, respectively. Although exceptions are noted and although predicting long-term prognosis based on these findings is difficult, this research may lead the way to curative hematopoietic stem cell transplantation and gene therapy.  Further research is underway to identify WASp-associated proteins, such as WASp-interacting protein (WIP) and several Wiskott-Aldrich syndrome proteins verprolin homologous (WAVE). [17, 18, 19, 20]
The estimated incidence of Wiskott-Aldrich syndrome in the United States is 1 in 250,000 live male births. 
The frequency in the European population has been reported to be similar to that of the United States (1 in 250,000 live male births). A study from Switzerland reported the incidence of Wiskott-Aldrich syndrome is 4.1 cases per 1 million live births. The same study also examined the prevalence of Wiskott-Aldrich syndrome in several national registries (ie, Italy, Japan, Switzerland, Sweden) and found that this condition occurred in 2-8.8% of patients with primary immunodeficiencies.  A similar range has been documented in a national registry in Ireland, as well. 
Morbidity and mortality have gradually improved with better antibiotics, advances in blood banking, better supportive care, and the ability to successfully provide immune reconstitution by stem cell transplantation. Median survival has increased from 8 months in patients born before 1935 to longer than 6 years in patients born after 1964.  In one case series, 94 surviving patients ranged in age from 1-35 years, with a median of 11 years; the average age of patients who died was 8 years. 
In one study the reported cause of death among patients who did not receive bone marrow transplants were infection (44%), bleeding (23%), or malignancy (26%).  Younger patients are more likely to die from bleeding, children are more likely to die from infection, and children and young adults die most often from malignancies. Malignancies may occur in children but are more frequent in affected adults. Lymphomas occur in 26% of patients aged 20 years and older. In one series, 12% of patients developed malignancies, primarily lymphoreticular tumors, and leukemia. In that series, the relative risk of malignancy was more than 100-fold that of normal and the risk increased with age. 
The average lifespan for patients who do not receive immune reconstitution is the second to third decade of life, although patients have survived into the fifth decade of life. Following major histocompatibility complex (MHC)–matched stem cell transplantation, the patient who escapes graft versus host disease (GVHD) usually has completely normal immune function and, therefore, has an excellent prognosis for normal survival.  Survival rates after stem cell transplant have continued to improve, particularly after more recent emphasis on performing these procedures as soon as possible after diagnosis. 
Wiskott-Aldrich syndrome has been reported in individuals of European, African, and Asian ancestry; however, Blacks and Asians are less likely to be affected. One large series of 301 cases of Wiskott-Aldrich syndrome from 149 families reported that 8 families were black and 4 families were Chicano.  Of the 40 families whose ancestry was traced outside North America, 38 emigrated from Europe.
More than 90% of affected patients are male, but females have been reported in the literature. Females typically have no family history. In some cases, females have been shown to have nonrandom inactivation of the X chromosome bearing the functional Wiskott-Aldrich syndrome allele. 
Age at presentation ranges from birth to 25 years. In one review, the average age of presentation was 21 months. [2, 21] Male infants present at birth with petechiae and ecchymoses. Infections usually begin in early infancy after maternal immunoglobulin G (IgG) is lost during the first 3 months of life. The frequency of infections usually increase with age. Patients are especially susceptible to encapsulated organisms. Eczema develops during the first year of life and resembles classic atopic dermatitis. Malignancies may occur in children but are more frequent in affected adults. Lymphomas occur in 26% of patients aged 20 years and older.
Loyola Presa JG, de Carvalho VO, Morrisey LR, Bonfim CM, Abagge KT, Vasselai A, et al. Cutaneous manifestations in patients with Wiskott-Aldrich syndrome submitted to haematopoietic stem cell transplantation. Arch Dis Child. 2013 Apr. 98(4):304-7. [Medline].
Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA. A multiinstitutional survey of the Wiskott-Aldrich syndrome. J Pediatr. 1994 Dec. 125(6 Pt 1):876-85. [Medline].
Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999 Dec. 93(3):190-7. [Medline].
Thrasher AJ. New insights into the biology of Wiskott-Aldrich syndrome (WAS). Hematology Am Soc Hematol Educ Program. 2009. 132-8. [Medline].
Candotti F. Clinical Manifestations and Pathophysiological Mechanisms of the Wiskott-Aldrich Syndrome. J Clin Immunol. 2018 Jan. 38 (1):13-27. [Medline].
Blundell MP, Bouma G, Calle Y, Jones GE, Kinnon C, Thrasher AJ. Improvement of migratory defects in a murine model of Wiskott-Aldrich syndrome gene therapy. Mol Ther. 2008 May. 16(5):836-44. [Medline].
Cagdas D, Aytac S, Kuskonmaz B, Ariga T, van der Burg M, Cetinkaya DU, et al. Low T Cell Numbers Resembling T-B+ SCID in a Patient with Wiskott-Aldrich Syndrome and the Outcome of Two Hematopoietic Stem Cell Transplantations. J Clin Immunol. 2017 Jan. 37 (1):18-21. [Medline].
Davis BR, Yan Q, Bui JH, Felix K, Moratto D, Muul LM, et al. Somatic mosaicism in the Wiskott-Aldrich syndrome: Molecular and functional characterization of genotypic revertants. Clin Immunol. 2010 Jan 31. [Medline].
Snapper SB, Meelu P, Nguyen D, Stockton BM, Bozza P, Alt FW. WASP deficiency leads to global defects of directed leukocyte migration in vitro and in vivo. J Leukoc Biol. 2005 Jun. 77(6):993-8. [Medline].
Morales-Tirado V, Sojka DK, Katzman SD, Lazarski CA, Finkelman FD, Urban JF, et al. Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function. Blood. 2009 Dec 23. [Medline].
Notarangelo LD, Miao CH, Ochs HD. Wiskott-Aldrich syndrome. Curr Opin Hematol. 2008 Jan. 15(1):30-6. [Medline].
Gulacsy V, Freiberger T, Shcherbina A, et al. Genetic characteristics of eighty-seven patients with the Wiskott-Aldrich syndrome. Mol Immunol. 2011 Feb. 48(5):788-92. [Medline].
Albert MH, Notarangelo LD, Ochs HD. Clinical spectrum, pathophysiology and treatment of the Wiskott-Aldrich syndrome. Curr Opin Hematol. 2010 Nov 11. [Medline].
Kwan SP, Hagemann TL, Blaese RM, Rosen FS. A high-resolution map of genes, microsatellite markers, and new dinucleotide repeats from UBE1 to the GATA locus in the region Xp11.23. Genomics. 1995 Sep 1. 29(1):247-52. [Medline].
Snapper SB, Rosen FS. The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization. Annu Rev Immunol. 1999. 17:905-29. [Medline].
Bastida JM, Del Rey M, Revilla N, Benito R, Perez-Andrés M, González B, et al. Wiskott-Aldrich syndrome in a child presenting with macrothrombocytopenia. Platelets. 2016 Nov 25. 1-4. [Medline].
Anton IM, Jones GE. WIP: a multifunctional protein involved in actin cytoskeleton regulation. Eur J Cell Biol. 2006 Apr. 85(3-4):295-304. [Medline].
Konno A, Kirby M, Anderson SA, Schwartzberg PL, Candotti F. The expression of Wiskott-Aldrich syndrome protein (WASP) is dependent on WASP-interacting protein (WIP). Int Immunol. 2007 Feb. 19(2):185-92. [Medline].
Soderling SH, Scott JD. WAVE signalling: from biochemistry to biology. Biochem Soc Trans. 2006 Feb. 34(Pt 1):73-6. [Medline].
Takenawa T, Suetsugu S. The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat Rev Mol Cell Biol. 2007 Jan. 8(1):37-48. [Medline].
Perry GH, Spector BD, Schuman LM. The Wiskitt-Aldrich syndrome inthe United States and Canada. J Pediatr. 1980. 97:72.
Ryser O, Morell A, Hitzig WH. Primary immunodeficiencies in Switzerland: first report of the national registry in adults and children. J Clin Immunol. 1988 Nov. 8(6):479-85. [Medline].
Abuzakouk M, Feighery C. Primary immunodeficiency disorders in the Republic of Ireland: first report of the national registry in children and adults. J Clin Immunol. 2005 Jan. 25(1):73-7. [Medline].
Mullen CA, Anderson KD, Blaese RM. Splenectomy and/or bone marrow transplantation in the management of the Wiskott-Aldrich syndrome: long-term follow-up of 62 cases. Blood. 1993 Nov 15. 82(10):2961-6. [Medline]. [Full Text].
Kobayashi R, Ariga T, Nonoyama S, Kanegane H, Tsuchiya S, Morio T. Outcome in patients with Wiskott-Aldrich syndrome following stem cell transplantation: an analysis of 57 patients in Japan. Br J Haematol. 2006 Nov. 135(3):362-6. [Medline].
Parolini O, Ressmann G, Haas OA, Pawlowsky J, Gadner H, Knapp W. X-linked Wiskott-Aldrich syndrome in a girl. N Engl J Med. 1998 Jan 29. 338(5):291-5. [Medline].
Peacocke M, Siminovitch KA. Wiskott-Aldrich syndrome: new molecular and biochemical insights. J Am Acad Dermatol. 1992 Oct. 27(4):507-19. [Medline].
Chandrakasan S, Singh S, Dogra S, Delaunay J, Proust A, Minz RW. Wiskott-Aldrich syndrome presenting with early onset recurrent acute hemorrhagic edema and hyperostosis. Pediatr Blood Cancer. 2011 Jul 1. 56(7):1130-2. [Medline].
Takimoto T, Takada H, Ishimura M, Kirino M, Hata K, Ohara O, et al. Wiskott-Aldrich syndrome in a girl caused by heterozygous WASP mutation and extremely skewed X-chromosome inactivation: a novel association with maternal uniparental isodisomy 6. Neonatology. 2015. 107(3):185-90. [Medline].
Ochs HD, Thrasher AJ. The Wiskott-Aldrich syndrome. J Allergy Clin Immunol. 2006 Apr. 117(4):725-38; quiz 739. [Medline].
Suri D, Singh S, Rawat A, Gupta A, Kamae C, Honma K, et al. Clinical profile and genetic basis of Wiskott-Aldrich syndrome at Chandigarh, North India. Asian Pac J Allergy Immunol. 2012 Mar. 30(1):71-8. [Medline].
Navabi B, Upton JE. Primary immunodeficiencies associated with eosinophilia. Allergy Asthma Clin Immunol. 2016. 12:27. [Medline].
Patiroglu T, Klein C, Gungor HE, Ozdemir MA, Witzel M, Karakukcu M, et al. CLINICAL FEATURES AND GENETIC ANALYSIS OF SIX PATIENTS WITH WISKOTT-ALDRICH SYNDROME REPORTING TWO NOVEL MUTATIONS: EXPERIENCE OF ERCIYES UNIVERSITY, KAYSERI, TURKEY. Genet Couns. 2016. 27 (1):9-24. [Medline].
Zhao Q, Zhang ZY, Zhao XD, Jiang LP, Zhao Y, Yang XQ. [Analysis of prenatal diagnosis for seven high-risk fetuses with Wiskott-Aldrich syndrome]. Zhonghua Er Ke Za Zhi. 2012 Jan. 50(1):15-9. [Medline].
Kang HJ, Shin HY, Ko SH, et al. Unrelated bone marrow transplantation with a reduced toxicity myeloablative conditioning regimen in Wiskott-Aldrich syndrome. J Korean Med Sci. 2008 Feb. 23(1):146-8. [Medline].
Hacein-Bey Abina S, Gaspar HB, Blondeau J, Caccavelli L, Charrier S, Buckland K, et al. Outcomes following gene therapy in patients with severe Wiskott-Aldrich syndrome. JAMA. 2015 Apr 21. 313(15):1550-63. [Medline].
Dupre L, Marangoni F, Scaramuzza S, et al. Efficacy of gene therapy for Wiskott-Aldrich syndrome using a WAS promoter/cDNA-containing lentiviral vector and nonlethal irradiation. Hum Gene Ther. 2006 Mar. 17(3):303-13. [Medline].
Galy A, Roncarolo MG, Thrasher AJ. Development of lentiviral gene therapy for Wiskott Aldrich syndrome. Expert Opin Biol Ther. 2008 Feb. 8(2):181-90. [Medline].
Castiello MC, Scaramuzza S, Pala F, Ferrua F, Uva P, Brigida I, et al. B-cell reconstitution after lentiviral vector-mediated gene therapy in patients with Wiskott-Aldrich syndrome. J Allergy Clin Immunol. 2015 Mar 16. [Medline].
Lacy CF, Armstrong LL, Goldman MP, Lance LL, eds. Drug Information Handbook 2008-2009. 16th ed. Cleveland, OH: Lexi-Comp Inc; 2008.
Hooper JA. Intravenous Immunoglobulins: Evolution of Commercial IVIG Preparations. Immunol Allergy Clin North Am. 2008 Nov. 28(4):765-78. [Medline].
Shah S. Pharmacy considerations for the use of IGIV therapy. Am J Health Syst Pharm. 2005 Aug 15. 62(16 Suppl 3):S5-11. [Medline].
Siegel J. The product: All intravenous immunoglobulins are not equivalent. Pharmacotherapy. 2005 Nov. 25(11 Pt 2):78S-84S. [Medline].
Kroger AT, Atkinson WL, Marcuse EK, Pickering LK. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006 Dec 1. 55:1-48. [Medline]. [Full Text].
Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins for persons with altered immunocompetence. MMWR Recomm Rep. 1993 Apr 9. 42:1-18. [Medline]. [Full Text].
Chen N, Zhang ZY, Liu DW, Liu W, Tang XM, Zhao XD. The clinical features of autoimmunity in 53 patients with Wiskott-Aldrich syndrome in China: a single-center study. Eur J Pediatr. 2015 Apr 16. [Medline].
Ngwube A, Hanson IC, Orange J, Rider NL, Seeborg F, Shearer W, et al. Outcomes after Allogeneic Transplant in Patients with Wiskott-Aldrich Syndrome. Biol Blood Marrow Transplant. 2018 Mar. 24 (3):537-541. [Medline].
Cianferoni A, Massaad M, Feske S, et al. Defective nuclear translocation of nuclear factor of activated T cells and extracellular signal-regulated kinase underlies deficient IL-2 gene expression in Wiskott-Aldrich syndrome. J Allergy Clin Immunol. 2005 Dec. 116(6):1364-71. [Medline].
Dam T, Danelishvili L, Wu M, Bermudez LE. The fadD2 Gene Is Required for Efficient Mycobacterium avium Invasion of Mucosal Epithelial Cells. J Infect Dis. 2006 Apr 15. 193(8):1135-42. [Medline].
de Saint Basile G, Lagelouse RD, Lambert N, et al. Isolated X-linked thrombocytopenia in two unrelated families is associated with point mutations in the Wiskott-Aldrich syndrome protein gene. J Pediatr. 1996 Jul. 129(1):56-62. [Medline].
Derry JM, Kerns JA, Weinberg KI, et al. WASP gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia. Hum Mol Genet. 1995 Jul. 4(7):1127-35. [Medline].
Derry JM, Ochs HD, Francke U. Isolation of a novel gene mutated in Wiskott-Aldrich syndrome [published erratum appears in Cell 1994 Dec 2;79(5):following 922]. Cell. 1994 Aug 26. 78(4):635-44. [Medline].
Dupuis-Girod S, Medioni J, Haddad E, et al. Autoimmunity in Wiskott-Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients. Pediatrics. 2003 May. 111(5 Pt 1):e622-7. [Medline]. [Full Text].
Eijkhout HW, van Der Meer JW, Kallenberg CG, et al. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med. 2001 Aug 7. 135(3):165-74. [Medline]. [Full Text].
Lutskiy MI, Shcherbina A, Bachli ET, Cooley J, Remold-O’Donnell E. WASP localizes to the membrane skeleton of platelets. Br J Haematol. 2007 Oct. 139(1):98-105. [Medline].
Mullen CA, Anderson KD, Blaese RM. Splenectomy and/or bone marrow transplantation in the management of the Wiskott-Aldrich syndrome: long-term follow-up of 62 cases. Blood. 1993 Nov 15. 82(10):2961-6. [Medline].
Ochs HD, Rosen FS. The Wiskott-Aldrich syndrome. Ochs HD, Smith CIE, Puck J, eds. Primary Immunodeficiency Diseases: a Molecular and Genetic Approach. New York, NY: Oxford University Press; 1999. 292-305.
Olivier A, Jeanson-Leh L, Bouma G, et al. A partial down-regulation of WASP is sufficient to inhibit podosome formation in dendritic cells. Mol Ther. 2006 Apr. 13(4):729-37. [Medline].
Samarin SN. WASP family proteins act between cytoskeleton and cellular signaling pathways. Biochemistry (Mosc). 2005 Dec. 70(12):1305-9. [Medline].
Tsuboi S, Nonoyama S, Ochs HD. Wiskott-Aldrich syndrome protein is involved in alphaIIbbeta3-mediated cell adhesion. EMBO Rep. 2006 Mar 31. [Medline].
Tsuji Y, Imai K, Kajiwara M, et al. Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team. Bone Marrow Transplant. 2006 Mar. 37(5):469-77. [Medline].
Wietstruck PMA, Zuniga CP, Talesnik GE, Mendez RC, Barriga CF. [Hematopoietic stem cell transplantation for patients with Wiskott-Aldrich syndrome]. Rev Med Chil. 2007 Jul. 135(7):917-23. [Medline].
Xie JW, Zhang ZY, Wu JF, Liu DW, Liu W, Zhao Y, et al. In vivo reversion of an inherited mutation in a Chinese patient with Wiskott-Aldrich syndrome. Hum Immunol. 2015 Apr 8. [Medline].
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% solution: 10% sucrose, < 20 mg NaCl/g protein
Lyophilized powder 3%, 6%, 9%, 12%
Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization
Sucrose free, contains 5% D-sorbitol
Gammagard Liquid 10%
Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation
Ready-for-use Liquid 10%
Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation
Contains no sugar, contains glycine
Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation
Contains sorbitol (40 mg/mL); do not administer if fructose intolerant
Ready-for-use solution 5%
Cohn-Oncley fraction II/III; ultrafiltration; pasteurization
5% solution: 5% glucose, 0.3% NaCl
Lyophilized powder 5%
(Baxter Bioscience for the American Red Cross)
Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated
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
(Swiss Red Cross for the American Red Cross)
Kistler-Nitschmann fractionation; pH 4, trace pepsin, nanofiltration
Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl
Lyophilized powder 3%, 6%, 9%, 12%
Privigen Liquid 10%
Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration
L-proline (~250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose)
Ready-for-use liquid 10%
Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration
Disclosure: Nothing to disclose.
Robyn Siperstein, MD Staff Physician, Department of Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
David J Valacer, MD
David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American Thoracic Society, New York Academy of Sciences
Disclosure: Nothing to disclose.
Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter’s University Hospital
Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology
Disclosure: Nothing to disclose.
James M Oleske, MD, MPH François-Xavier Bagnoud Professor of Pediatrics, Director, Division of Pulmonary, Allergy, Immunology and Infectious Diseases, Department of Pediatrics, Rutgers New Jersey Medical School; Professor, Department of Quantitative Methods, Rutgers New Jersey Medical School
James M Oleske, MD, MPH is a member of the following medical societies: Academy of Medicine of New Jersey, American Academy of Allergy Asthma and Immunology, American Academy of Hospice and Palliative Medicine, American Association of Public Health Physicians, American College of Preventive Medicine, American Pain Society, Infectious Diseases Society of America, Infectious Diseases Society of New Jersey, Medical Society of New Jersey, Pediatric Infectious Diseases Society, Arab Board of Family Medicine, American Academy of Pain Management, National Association of Pediatric Nurse Practitioners, Association of Clinical Researchers and Educators, American Academy of HIV Medicine, American Thoracic Society, American Academy of Pediatrics, American Public Health Association, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Ann O’Neill Shigeoka, MD to the development and writing of this article.
Pediatric Wiskott-Aldrich Syndrome
Research & References of Pediatric Wiskott-Aldrich Syndrome|A&C Accounting And Tax Services