Background
Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder originally described as a clinical triad of thrombocytopenia, [1] 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, [2, 3] and, since then, about 300 mutations have been reported. [4]
Other Medscape Reference articles on Wiskott-Aldrich syndrome include Wiskott-Aldrich Syndrome and Pediatric Wiskott-Aldrich Syndrome.
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.
Etiology
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. [5]
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. [6] WASp expression in dendritic cells regulates both the ability to traffic to secondary lymphoid organs and to activate naive T cells in lymph nodes. [7, 8]
Eczema appears to be related to the abnormal function of the T cells.
Epidemiology
Frequency
The prevalence of Wiskott-Aldrich syndrome is approximately 4 cases per 1 million births. [9]
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. [10]
Age
Thrombocytopenia and platelet dysfunction can be found from birth, with dermatitis following in a few months.
Prognosis
Death usually occurs during infancy. Death usually occurs during the first decade, although survival to 18 years has been recorded. The cause of death in Wiskott-Aldrich syndrome is infection in 55-60% of patients, bleeding in 24-27% of patients, and lymphoreticular malignancy in about 5-10% of patients. Ten percent of Wiskott-Aldrich syndrome patients die from lymphoreticular malignancy, usually as adolescents or young adults.
-
Eczematous lesions in Wiskott-Aldrich syndrome. The lesion is essentially indistinguishable from that of atopic dermatitis except for the presence of purpura and petechiae.
-
A bloody crust can be seen on the red papules.
