1. The Wiskott-Aldrich Syndrome: An X-linked Primary Immunodeficiency
Kristin Goff

2. WAS Primary immune deficiency disorder X-linked recessive trait
Entails part of the bodies immune system is missing or does not function properly
Caused by genetic defects in the immune system
X-linked recessive trait
Genetic defect causing deficiency is on the X-chromosome
Only affects males and is passed to child from the mother, a healthy carrier of the disorder

5. Symptoms
Thrombocytopenia (low platelet count and disturbed platelet function)
Recurrent infections
Eczema
Malignancies in the form of leukemia and lymphoma occur in more severe cases

6. Normal platelets

7. Small Platelets

8. History First described by German physician Alfred Wiskott in 1937
Robert Anderson Aldrich described the disease as an X-linked recessive trait in 1954
Joined the list of Primary Immune Deficiency Diseases in the 1960’s

9. Mutations
WAS is associated with the absence of the Wiskott-Aldrich Syndrome protein (WASP) which is caused by simple mutations in the WASP gene
Missense and frameshift mutations are two known to cause WAS

10. A missense mutation has the ability to
change one amino acid into a different
amino acid, altering the protein and
possibly causing it to be nonfunctional.
A frameshift mutation deletes a DNA
base, shifting the entire sequence
and changing the amino acids from
that point on. In this case, the
Mutation turns an amino acid in
the protein sequence into a stop
codon and translation of the protein is
prematurely ended.

11. Actin Reorganization
WASP is involved in the reorganization of the actin skeleton. When the WAS protein is altered, it does not properly bind and actin reorganization is prohibited.

12. Affect on T Lymphocytes
Cytoskeleton reorganization is involved in the binding of T lymphocytes to antigen-presenting cells through CD3 crosslinking.
Without actin reorganization, CD3 is not properly presented at the cells surface and the T cell is not activated.
Causes recurrent viral and fungal infections (as noted in symptoms).

14. Affect on B Lymphocytes
Thymus dependent B lymphocytes need T cells for activation and differentiation.
B cells only able to produce IgM through thymus independent B lymphocytes.
Causes recurrent bacterial infections because proper antibodies are not produced against certain bacteria.

17. Treatment Intravenous immunoglobulin substitution
Specialized antibiotics
Splenectomy
Hematopoietic stem cell transplantation

18. WAS Discovered in Females
Skewed X-chromosome inactivation in a female carrier can cause the typically healthy female to exhibit clinical signs of the disorder.
Causes the X-chromosome carrying the normal WASP gene to become inactivated so only the X-chromosome with the mutant WASP gene is left active.

19. Summary WAS is caused by a mutation in the WASP gene.
A mutation in the WASP gene inhibits actin reorganization.
Without actin reorganization, CD3 cannot be presented and T cells are not activated.
Thymus dependent B cells are not activated without production of T cells.
B cell differentiation does not occur and only IgM antibodies are produced.