Review Question - QID 107249

This patient's presentation of eczema, recurrent infections, and thrombocytopenia is consistent with a diagnosis of Wiskott-Aldrich syndrome. Wiskott-Aldrich syndrome (WAS) is associated with low levels of CD43 expression on lymphocytes.

Wiskott-Aldrich syndrome is an X-linked recessive disorder that results in partial B and T cell deficiencies through a defective cytoskeletal glycoprotein. It is associated with a decreased platelet count, increased IgE and IgA, and decreased IgM. Additionally, these patients exhibit a defective CD43 molecule. Treatment involves antibiotics, IVIG, and, more recently, gene therapy.

Davutoglu et al. discuss a case of Wiskott-Aldrich syndrome that presented as recurrent fever, petechiae, cutaneous infections, diarrhea, and purulent otitis in an 11-month old boy. Given the wide variation in the phenotypic presentation of this disorder, diagnosis is often confirmed via genetic analysis or determination of protein expression with a specific antibody.

Hacein-Bey Abina et al. studied gene therapy outcomes in patients with severe Wiskott-Aldrich syndrome. They analyzed 7 patients with severe WAS who received gene-corrected hematopoietic stem cell transplantation, with follow-up from 9 to 42 months. One patient died due to an infection. The remaining 6 patients showed resolution of eczema, decreased susceptibility to infection, and no major bleeding episodes. In the two years after treatment, hospitalization days were reduced to 0 from a median of 25 days prior to treatment.

Illustration A summarizes the clinical manifestations and genetic pathologies in WAS. Illustration B shows how gene therapy is administered in patients with severe WAS.

Incorrect Answers:
Answer 1: Defective CD18 is seen in leukocyte adhesion deficiency.
Answer 3: Decreased CD8 counts are seen in MHC class I deficiency.
Answer 4: Wiskott-Aldrich syndrome is associated with decreased IgM levels.
Answer 5: Wiskott-Aldrich syndrome is associated with increased IgE and IgA levels.