Wiskott-Aldrich Syndrome

Key Features

Essentials of Diagnosis

• Immunodeficiency with recurrent infections

• Microplatelet thrombocytopenia

• Eczema

• Occurs only in males

General Considerations

• Characterized by immunodeficiency, microplatelet thrombocytopenia, and eczema

• Results from mutations of the gene encoding WAS protein (WASP) at X11p

• WASP is a protein involved in the rearrangement of actin and is important in interactions between T lymphocytes and antigen-presenting cells

Clinical Findings

Symptoms and Signs

• Common presenting symptoms include mucosal bleeding, bloody diarrhea, cerebral hemorrhage, and severe infections with polysaccharide-encapsulated bacteria

• Clinical presentation can vary from classic severe Wiskcott-Aldrich syndrome to mild thrombocytopenia without immunodeficiency, or X-linked thrombocytopenia, depending on the mutation

• Malignancies and autoimmune syndromes can develop over time

Differential Diagnosis

• Idiopathic thrombocytopenic purpura

• Leukemia

• Myelodysplasia

• Drug adverse effect

• Infection

Diagnosis

Laboratory Findings

• Low platelet count

• Small platelets

• Low or absent isohemagglutinins

• Reduced antibody responses to polysaccharide antigens (Streptococcus pneumoniae and Haemophilus influenzae)

• IgM may be low

• IgG is usually normal

• IgA and IgE are often high

Diagnostic Procedure

• Diagnosis can be confirmed by genetic testing for a mutation of the WASP gene or by assessing WASP expression

• Genetic testing can also be used for carrier screening

Treatment

• Infection prophylaxis with antibiotics (including trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia)

• IVIg-replacement therapy for patients with deficient antibody responses

• Splenectomy to reduce thrombocytopenia has been helpful in some patients with X-linked thrombocytopenia, but it must be followed by antibiotic prophylaxis because of the increased risk of septicemia and sudden death

• Platelet transfusions should be avoided unless severe bleeding has occurred

• Finally, bone marrow transplantation using the best-matched donor offers the possibility of a definitive cure, but it is associated with morbidity and mortality

Outcome

Prognosis

• Left untreated, survival beyond adolescence is rare

Reference