Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome (WAS) is a rare immunodeficiency disease with a characteristic phenotype that includes:

• X-linked recessive
• petechiae, bloody diarrhea, epistaxis due to thrombocytopenia with small platelets
• eczema starts in first month of life
• recurrent infections with encapsulated bacteria due to immunodeficiency
• increased incidence of autoimmune manifestations and malignancies 

Epidemiology

The incidence currently quoted is approximately 4 per million live male births, although there can be regional variation. Rarely occurs in females.

Pathology

The pathophysiology relates to structural mutation with defective actin polymerization in hematopoietic cells as a result of deficient or dysregulated activity of the Wiskott-Aldrich syndrome protein (WASp) which has multiple functions. There is a poor antibody response to polysaccharide antigens. Low IgM, but high IgA and IgE levels.

Genetics

It is mostly an X-linked recessive condition.

Associations

• splenic hamartoma
• infantile cortical hyperostosis ³

Complications

• may predispose to malignancies such as primary CNS lymphoma

Treatment and prognosis

The severity of disease is variable and can be predictable from the genotype to a certain degree. Bone marrow transplantation may be the only definitive treatment ⁵.

History and etymology

It was originally described by Wiskott in 1937 as a triad of ear discharge, eczema and thrombocytopenia. The genetics, i.e. X-linked recessive disorder, were described by Aldrich ⁷ in 1954.