Wiskott–Aldrich syndrome

Wiskott-Aldrich syndrome (WAS) is a rare, X-linked immune disorder expressed only in males due to its recessive nature. Males express the disease after receiving a single allele with the mutation, as the gene is not present on the Y allele, and so no dominant allele is present to mask the expression. The disorder is a result of mutations in the WAS gene, which is responsible for the production of the WAS protein (WASp). As a direct effect of these mutations, issues arise with cellular signaling, B and T cell function, and formation of the immunological synapse. Manifestations of the disorder arise as thrombocytopenia (due to abnormal cytoskeleton arrangement in hematopoietic cells and lack of invariant natural killer T cells), immunodeficiency (due to impaired immune cell function, interaction, and tolerance), and an increased risk of cancers such as leukemia and lymphoma (because of impaired T-cell and NK-cell immune surveillance).  

Hematopoietic cell transplant replaces the patient’s defective immune cells and hematopoietic system with healthy donor stem cells, allowing the bone marrow to reproduce normal immune cells and platelets, the only proven cure for Wiskott-Aldrich syndrome to date. Gene therapy is another emerging treatment that repairs the patient’s own stem cells by replacing a functional WAS gene in place of the defective one and reinfusing these corrected cells back into the body.

References

Malik, M. A. (2023, June 26). Wiskott-Aldrich syndrome. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK539838/

Aldrich Foundation - Treatment. Wiskott. (n.d.). https://www.wiskott.org/About-WAS/treatment-of-was

Braun, C. J., Witzel, M., Paruzynski, A., Boztug, K., von Kalle, C., Schmidt, M., & Klein, C. (2014, October 30). Gene therapy for Wiskott-Aldrich syndrome-long-term reconstitution and clinical benefits, but increased risk for leukemogenesis. Rare diseases (Austin, Tex.). https://pmc.ncbi.nlm.nih.gov/articles/PMC4755244/