Wiskott-Aldrich Syndrome

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PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

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Synonym: Wiskott-Aldrich-Huntley syndrome

This is an X-linked recessive condition with immunodeficiency as an underlying problem. An autosomal dominant form has also been described.[1] It is characterised by:[2]

Wiskott-Aldrich syndrome (WAS) was first described by Wiskott in Germany in 1937[3] and later by Aldrich in the USA in 1954.[4] However, descriptions of the condition go back to the 19th century.[5]

  • The underlying mutation is in the gene for the Wiskott-Aldrich syndrome protein (WASP) on the X-chromosome at Xp11.22-23.[6]
  • WASP is needed for normal antibody function, T-cell responses and platelet production.

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  • The incidence of the classic syndrome is estimated to be between one and ten in one million individuals, although it is likely to be higher.[7]
  • Being X-linked and potentially lethal, it would be expected almost invariably to affect males and more than 90% of affected patients are male. However, affected females have been reported.
  • Affected females usually have no family history and some have been shown to have nonrandom inactivation of the X chromosome bearing the functional Wiskott-Aldrich syndrome (WAS) allele.

Presentation can be any time from birth to 25 years but most cases present in the first 2 years of life. Less than one third of affected individuals have the full triad at presentation but almost 90% present with features of thrombocytopenia. Around 5% present only with infection and 20% only with haematological problems.[8]

  • Bleeding problems:
    • Petechiae and ecchymoses can occur.These may be around the oral mucosa.
    • Bloody diarrhoea is quite common.
    • There may be bleeding from the umbilical stump or after circumcision.
    • In fewer than 2% there is intracranial haemorrhage. This may happen at birth, possibly from the trauma of delivery.
  • Infections:
  • Eczema:
    • This tends to develop during the first year of life and it is clinically similar to atopic eczema.
    • However, it presents earlier than usual and may be worse during infection.
    • There may be other atopic conditions such as allergic rhinitis.
  • Autoimmune disease:
  • Malignancy:
    • This may occur in children but is more common in adults.
    • Around a quarter of those over 20 years develop lymphoma.
    • Leukaemia may also occur but the most common malignancy is non-Hodgkin's lymphoma.
  • Low platelet count (≤70 x 109/L).[2]
  • Low mean platelet volume (<5fL).
  • Low IgG and IgM levels with elevated IgA and IgE (values need to be interpreted for age).
  • Testing may show impairment of cell-mediated immunity.
  • Autoantibodies may be detected if autoimmune disease is present, especially in autoimmune haemolytic anaemia and immune thrombocytopenia and neutropenia.
  • Consider the diagnosis in boys with thrombocytopenia. Detection of the Wiskott-Aldrich syndrome protein (WASP) can facilitate the diagnosis.[10]
  • Bacteriology is required to help treat infection.
  • Chest X-ray may be indicated depending on infective symptoms.
  • Renal and liver function should be monitored.
  • Tissue typing of the patient and close family members may be indicated if stem cell transplantation is considered.
  • Carrier females may have low platelet counts.[11]

General

  • All immunisations should be given as usual. Hib is especially important.
  • Encourage normal work and school but avoid contact sports.

Medical management

  • Infections will need appropriate antibiotics. Infusion of immunoglobulin may also be required.
  • Bleeding may require transfusion of packed red cells and platelets. Blood should be low in white cells to reduce the risk of isoimmunisation, as a stem cell transplant may be required in the future.
  • Skin disease should be treated, including treating eczema with moisturising creams and topical steroid preparations as indicated.
  • If there is exposure to chickenpox, immunoglobulin or antivirals such as aciclovir are indicated. Varicella vaccine may be protective.
  • In severe thrombocytopenia, splenectomy may be indicated but this also increases the risk of infection. Prophylactic antibiotics and immunisation (pneumococcal, Hib and meningococcal) are needed.[2]
  • Autoimmune diseases are managed in the normal way.

Potential cure

  • Stem cell transplant can offer the chance of cure. It may be successful in over 90% of cases.[2][12]
  • In the future, gene therapy may also be an option.[13]
  • Recurrent infections as outlined above.
  • Bleeding can be difficult to control and intracranial bleeding may occur.
  • Chronic renal disease may be associated with autoimmune disease.
  • Haematological malignancy, especially non-Hodgkin's lymphoma.
  • Graft-versus-host disease and other complications from stem cell-transplantation.
  • The prognosis has improved enormously over the years due to improved control of infection, transfusion services and stem cell transplantation.
  • If stem cell transplantation is not carried out, individuals usually survive until their second or third decade and die from bleeding, malignancy or infection.[2]
  • Successful stem cell transplantation can mean reversal to normal immune function and the potential for a normal life span.[2]
  • A recent multicentre study looked at long-term outcome following stem cell transplantation in Wiskott-Aldrich syndrome (WAS). Amongst 96 patients, three patients died 2.1 to 21 years following transplantation. Overall 7-year event-free survival rate was 75%.[14]
  • This can detect mutations in the Wiskott-Aldrich syndrome protein (WASP) gene in those with a family history of Wiskott-Aldrich syndrome (WAS).
  • It may allow planning for Caesarean section to reduce the risk of intracranial bleeding due to birth trauma.
  • It may also allow planning for early stem cell transplantation, as this can improve prognosis.

Further reading & references

  1. Wiskott Aldrich Syndrome Autosomal Dominant, Online Mendelian Inheritance in Man (OMIM)
  2. Schwartz RA et al, Pediatric Wiskott-Aldrich Syndrome, Medscape, Sep 2010
  3. Wiskott, A; Familiarer, angeborener Morbus Werlhofii? Mschr. Kinderheilk. 68: 212-216, 1937
  4. Aldrich RA, Steinberg AG, Campbell DC; Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea. Pediatrics. 1954 Feb;13(2):133-9.
  5. Perry GS 3rd, Spector BD, Schuman LM, et al; The Wiskott-Aldrich syndrome in the United States and Canada (1892-1979). J Pediatr. 1980 Jul;97(1):72-8.
  6. Wiskott Aldrich Syndrome X-linked recessive #301000, Online Mendelian Inheritance in Man (OMIM)
  7. Thrasher AJ; New insights into the biology of Wiskott-Aldrich syndrome (WAS). Hematology Am Soc Hematol Educ Program. 2009:132-8.
  8. Sullivan KE, Mullen CA, Blaese RM, et al; A multiinstitutional survey of the Wiskott-Aldrich syndrome. J Pediatr. 1994 Dec;125(6 Pt 1):876-85.
  9. 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.
  10. Qasim W, Gilmour KC, Heath S, et al; Protein assays for diagnosis of Wiskott-Aldrich syndrome and X-linked thrombocytopenia. Br J Haematol. 2001 Jun;113(4):861-5.
  11. Van Den Bosch J, Drukker J; The Aldrich Syndrome - A clinical and genetic study of several Dutch families. Maandschr Kindergeneeskd. 1964 Jul;32:359-73.
  12. 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.
  13. Chinen J, Puck JM; Successes and risks of gene therapy in primary immunodeficiencies. J Allergy Clin Immunol. 2004 Apr;113(4):595-603; quiz 604.
  14. Ozsahin H, Cavazzana-Calvo M, Notarangelo LD, et al; Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation. Blood. 2008 Jan 1;111(1):439-45. Epub 2007 Sep 27.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Michelle Wright
Current Version:
Document ID:
2940 (v23)
Last Checked:
20/04/2011
Next Review:
18/04/2016

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