eMedicine Specialties > Dermatology > Pediatric Diseases

Wiskott-Aldrich Syndrome

Author: Akimichi Morita, MD, PhD, Professor, Chairman, Department of Dermatology, Nagoya City University Medical School, Japan
Contributor Information and Disclosures

Updated: Jan 30, 2009

Introduction

Background

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder originally described as a clinical triad of thrombocytopenia, eczema (atopiclike dermatitis), and recurrent pyogenic infections. Only 27% of patients have the classic triad, 20% of patients have hematologic manifestations alone, and 5% have infectious features before diagnosis. Recurrent infections result from immunodeficiency of both humoral immune responses and T-cell–mediated immune responses. The responsible gene (WASP) was identified in 1994.1

Other eMedicine articles on Wiskott-Aldrich syndrome include Wiskott-Aldrich Syndrome (Allergy and Immunology) and Wiskott-Aldrich Syndrome (Pediatrics).

Pathophysiology

Wiskott-Aldrich syndrome's hemorrhagic condition is due to both quantitative platelet defects and qualitative platelet defects. Thrombocytopenia is persistent. Platelets are small and fail to aggregate. Recurrent pyogenic infections are secondary to immunodeficiency of both humoral immune responses and T-cell–mediated immune responses. Eczema appears to be related to the abnormal function of the T cells.

Frequency

United States

The prevalence of Wiskott-Aldrich syndrome is approximately 4 cases per 1 million births.2

Mortality/Morbidity

Death in childhood is common. Death usually occurs during the first decade, although survival to 18 years has been recorded.

Race

Most Wiskott-Aldrich syndrome patients are white. Blacks and Asians are rarely affected.

Sex

Most Wiskott-Aldrich syndrome patients are male. One case was reported in a girl.3

Age

Thrombocytopenia and platelet dysfunction can be found from birth, with dermatitis following in a few months.

Clinical

History

  • Thrombocytopenia and platelet dysfunction are often present from birth in Wiskott-Aldrich syndrome.
  • Wiskott-Aldrich syndrome patients usually develop bleeding and bloody diarrhea during the first weeks or months of life. Hematuria, epistaxis, and cutaneous petechiae may appear.
  • The characteristic triad of thrombocytopenia, eczema, and recurrent infections generally becomes apparent during the first year of life.
  • Eczema usually appears during the first month and fulfills the Rajka and Hanifin diagnostic criteria for atopic dermatitis.
  • Recurrent bacterial infections begin in infancy as placentally transmitted maternal antibody levels diminish. Patients are susceptible to a wide variety of bacterial infections, including septicemia, pneumonia, meningitis, pansinusitis, conjunctivitis, furunculosis, otitis externa, and otitis media.

Physical

  • Eczema commonly develops in the scalp, on the face, in the flexures, and in the diaper area, although patients commonly have widespread involvement with progressive lichenification. The lesion is essentially indistinguishable from atopic dermatitis apart from the frequent presence of purpura and/or petechiae and excessive bleeding from excoriations. Serosanguineous crust may appear.
  • Immunoglobulin E (IgE)–mediated allergic diseases (eg, urticaria, food allergies, asthma) may appear.
  • Mucocutaneous petechiae may appear.
  • Spontaneous bleeding from the oral cavity and hematuria are common in Wiskott-Aldrich syndrome.
  • Secondary bacterial infection of eczematous lesions is common.
  • Hepatosplenomegaly is common in Wiskott-Aldrich syndrome.
  • Lymphadenopathy, transient arthritis, nephropathy, and nodular vasculitis are occasionally present in Wiskott-Aldrich syndrome.

Causes

  • Sialylated glycoprotein (CD43), a component of the T-cell activation pathway that binds intercellular adhesion molecule-1 (ICAM-1), is not stably expressed by lymphocytes and platelets; it was suspected to be the primary cause.4
  • Several mutations in the WASP gene, which consists of 12 exons and encodes 502 amino acids, have been identified in patients with Wiskott-Aldrich syndrome. WASP is an important transcription factor of lymphocyte and platelet function. It has been also shown that activating mutations of WASP are responsible for X-linked thrombocytopenia or myelodysplasia.
  • The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of actin polymerization in hematopoietic cells. Mutations in WASp cause a severe immunodeficiency characterized by defective initiation of primary immune response and autoimmunity. WASp expression in dendritic cells regulates both the ability to traffic to secondary lymphoid organs and to activate naive T cells in lymph nodes.5
  • Eczema appears to be related to the abnormal function of the T cells.

More on Wiskott-Aldrich Syndrome

Overview: Wiskott-Aldrich Syndrome
Differential Diagnoses & Workup: Wiskott-Aldrich Syndrome
Treatment & Medication: Wiskott-Aldrich Syndrome
Follow-up: Wiskott-Aldrich Syndrome
Multimedia: Wiskott-Aldrich Syndrome
References
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References

  1. Derry JM, Ochs HD, Francke U. Isolation of a novel gene mutated in Wiskott-Aldrich syndrome. Cell. Aug 26 1994;78(4):635-44. [Medline].

  2. Perry GS 3rd, Spector BD, Schuman LM, et al. The Wiskott-Aldrich syndrome in the United States and Canada (1892-1979). J Pediatr. Jul 1980;97(1):72-8. [Medline].

  3. Conley ME, Wang WC, Parolini O, Shapiro DN, Campana D, Siminovitch KA. Atypical Wiskott-Aldrich syndrome in a girl. Blood. Sep 1 1992;80(5):1264-9. [Medline].

  4. Silvin C, Belisle B, Abo A. A role for Wiskott-Aldrich syndrome protein in T-cell receptor-mediated transcriptional activation independent of actin polymerization. J Biol Chem. Jun 15 2001;276(24):21450-7. [Medline].

  5. Pulecio J, Tagliani E, Scholer A, et al. Expression of Wiskott-Aldrich syndrome protein in dendritic cells regulates synapse formation and activation of naive CD8+ T cells. J Immunol. Jul 15 2008;181(2):1135-42. [Medline].

  6. Yamada M, Ariga T, Kawamura N, et al. Determination of carrier status for the Wiskott-Aldrich syndrome by flow cytometric analysis of Wiskott-Aldrich syndrome protein expression in peripheral blood mononuclear cells. J Immunol. Jul 15 2000;165(2):1119-22. [Medline].

  7. Sellars WA, South MA. Wiskott-Aldrich syndrome with 18-year survival. Treatment with transfer factor. Am J Dis Child. May 1975;129(5):622-7. [Medline].

  8. 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. Nov 15 1993;82(10):2961-6. [Medline].

  9. 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. Mar 2006;17(3):303-13. [Medline].

  10. Corash L, Shafer B, Blaese RM. Platelet-associated immunoglobulin, platelet size, and the effect of splenectomy in the Wiskott-Aldrich syndrome. Blood. Jun 1985;65(6):1439-43. [Medline].

  11. Cotelingam JD, Witebsky FG, Hsu SM, Blaese RM, Jaffe ES. Malignant lymphoma in patients with the Wiskott-Aldrich syndrome. Cancer Invest. 1985;3(6):515-22. [Medline].

  12. Filipovich AH, Mathur A, Kamat D, Kersey JH, Shapiro RS. Lymphoproliferative disorders and other tumors complicating immunodeficiencies. Immunodeficiency. 1994;5(2):91-112. [Medline].

  13. Kwan SP, Hagemann TL, Radtke BE, Blaese RM, Rosen FS. Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene. Proc Natl Acad Sci U S A. May 9 1995;92(10):4706-10. [Medline].

  14. Notarangelo LD, Mori L. Wiskott-Aldrich syndrome: another piece in the puzzle. Clin Exp Immunol. Feb 2005;139(2):173-5. [Medline].

  15. Oda A, Ochs HD. Wiskott-Aldrich syndrome protein and platelets. Immunol Rev. Dec 2000;178:111-7. [Medline].

  16. Savoy DN, Billadeau DD, Leibson PJ. Cutting edge: WIP, a binding partner for Wiskott-Aldrich syndrome protein, cooperates with Vav in the regulation of T cell activation. J Immunol. Mar 15 2000;164(6):2866-70. [Medline].

  17. Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA. A multiinstitutional survey of the Wiskott-Aldrich syndrome. J Pediatr. Dec 1994;125(6 Pt 1):876-85. [Medline].

  18. 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. Mar 2006;37(5):469-77. [Medline].

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Further Reading

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Keywords

Wiskott-Aldrich syndrome, Wiskott-Aldrich-Huntley syndrome, eczema-thrombocytopenia syndrome, eczema-thrombocytopenia-diarrhea syndrome, eczema-thrombocytopenia immunodeficiency syndrome, X-linked disorders, thrombocytopenia, eczema, recurrent pyogenic infections

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Contributor Information and Disclosures

Author

Akimichi Morita, MD, PhD, Professor, Chairman, Department of Dermatology, Nagoya City University Medical School, Japan
Disclosure: Nothing to disclose.

Medical Editor

Jacek C Szepietowski, MD, PhD, Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland
Disclosure: Stiefel Salary Employment

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: 3M Pharmaceutical Grant/research funds Other; Graceway Pharmaceuticals Grant/research funds Other

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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