Wiskott-Aldrich Syndrome (WAS)

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology

Combined Immunodeficiencies (click to enlarge the image).

WAS is X-linked recessive.

WAS features

Eczema, thrombocytopenic purpura, immunodeficiency
Normal megakaryocytes but small defective platelets
Presentation is usually in infancy: prolonged bleeding from circumcision, hematochezia, or excessive bruising

WAS is due to mutations in WAS protein (WASP). WAS maps to Xp11.22-11.23. WASP expression is limited to lymphocytic and megakaryocytic lineages. WASP participates in actin polymerization. There is an isolated X-linked thrombocytopenia (only) due to WAS mutations.

WAS presentation

Prolonged bleeding from circumcision site
Bloody diarrhea
Excessive bruising
Atopic derm
Recurrent infection pneumococci

WAS is associated with small platelets – this is unusual because most bleeding disorders stimulate BM and often produce larger platelets.

Infections usually develops within the first year of life. WAS is associated with early infection with encapsulated organisms followed by opportunistic pathogens later in life. Survival beyond teens is rare. Infections and bleeding are usual causes of death. There is a 12% incidence of fatal malignancy.

Treatment and prognosis of WAS

BM transplant is the only definitive treatment option in WAS. Without transplant, patients with clinically severe WAS die in childhood. Splenectomy performed in the context of IVIG treatment and prophylactic antibiotics has proven beneficial if a BM donor is not available. The most common cause of death is EBV-induced lymphoreticular malignancy.

Successful Stem-Cell Gene Therapy for the Wiskott–Aldrich Syndrome was reported in the NEJM in 2010. This German study included 2 two patients who had this disorder and were treated with a transfusion of autologous, genetically modified hematopoietic stem cells (HSC).

There was a sustained expression of WAS protein expression in HSC, lymphoid and myeloid cells, and platelets after gene therapy. T and B cells, natural killer (NK) cells, and monocytes were functionally corrected.

After treatment, the patients' clinical condition markedly improved, with resolution of hemorrhagic diathesis, eczema, autoimmunity, and predisposition to severe infection.

Comprehensive insertion-site analysis showed vector integration that targeted multiple genes controlling growth and immunologic responses in a persistently polyclonal hematopoiesis.

Lentiviral vectors are expected to improve efficacy and safety of gene therapy for the Wiskott–Aldrich syndrome (http://goo.gl/gCH2P).

Conditions with elevated IgE

Atopic dermatitis, Asthma, ABPA, and allergic fungal sinusitis
Infections (parasites, HIV, TB, EBV, and CMV)
Malignancy (IgE myeloma and lymphoma)
Churg-Strauss syndrome
Kimura’s disease, painless, unilateral cervical lymphadenopathy or subcutaneous masses in the head or neck region

Immunodeficiency diseases with elevated IgE

Hyper IgE syndrome (HIES)
Wiskott-Aldrich syndrome (WAS)
Omenn syndrome
DiGeorge syndrome (DGS)
Netherton syndrome, form of ichthyosis associated with SPINK5
Nezelof syndrome, congenital hypoplasia of the thymus with retention of normal parathyroid function (in contrast to complete DiGeorge syndrome in which there is absence of the parathyroids)


Published: 08/29/2009
Updated: 10/12/2011


Anonymous said...

In the last para above treatment you have written "WAS is AD" isnt it X linked Recesive, or does AD stand for something else which I couldnt understand. Thanks

Allergy Cases said...

Thank you for your comment.

The text above clearly states that "WAS is X-linked recessive" condition rather than autosomal dominant. The paragraph which you mentioned was clarified.