Wiskott-Aldrich Syndrome is a rare X-linked immunodeficiency disease characterized by immunodeficiency, thrombocytopenia, and eczema. It is caused by mutations in the WAS protein gene which regulates actin cytoskeleton organization. This leads to defects in T-cells and B-cells, recurrent infections, bleeding issues, and increased cancer risk. The only cure is hematopoietic stem cell transplant from a matched sibling donor, while treatment focuses on antibiotics, platelet transfusions, and IVIG for antibody replacement.

1. Wiskott-Aldrich Syndrome
YASHWANT KUMAR DILLI BABU
GROUP-8
3rd YEAR.

2. Introduction and epidemiology
 Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency
disease
 Presents with three main symptoms (immunodeficiency,
thrombocytopenia and eczema)
 Caused by a mutation in the WAS protein (WASp) gene on
short arm of x-chromosome.
 Frequency of 4 cases per million
males worldwide and no geographical factor.
 Causes defects in both cellular and humoral immunity

3. HISTORY:
 First discovered by Dr. Alfred Wiskott in
1937
 Dr. Robert Aldrich demonstrated the X-
linked inheritance pattern in 1954
 The WAS gene was discovered in 1994
 Before 1937, life expectancy was only 8
months, but today the median life
expectancy is 20 years, with a range of
1-35 years (Ochs, 2011)

4. Target Organ
• WASP is a key regulator in hematopoietic
cells.
– All cells in the hematopoietic cell line are
affected.
– Primarily lymphocytes and platelets.
• T cell defect in the activation and TCR
engagement.
• The spleen is a secondary target since it
acts to remove the defective blood cells

5. Normal platelets

6. Small Platelets

7. 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.

8. 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).

10. 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.

11. Symptoms
• Thrombocytopenia (low
platelet count and
disturbed platelet
function)-causes
bleeding.
• Recurrent infections
• Even brusing and
petechia
• Eczema
• Malignancies in the form
of leukemia and
lymphoma occur in more
severe cases

12. DIAGNOSIS
• Genetic screening for mutation in the WASp gene after
identification by symptoms
• Immunologic abnormalities can be identified in children
>2 years.
– Used to support diagnosis.
– Fail to produce anybodies to some vaccinations.
– Skin Test to asses T cell function.
• WAS is suspected in any boy with unusual bleeding or
bruising with congenital or early onset thrombocytopenia.
• Cord blood can be taken to observe platelets and the
most useful diagnostically.
• Prenatal diagnosis.

13. Treatment
• Only cure is hematopoietic stem cell
transplant
– Matched sibling most successful
– Unrelated donor much more risky
– Greatest success when done <5yrs of age
• Lentiviral gene therapy.
• Bone marrow transplant.

15. Treatment for symptoms
– Prophylactic antibiotics
– Platelet transfusions(treat bleeding)
– Splenectomy(no longer used)
• Reverses the thrombocytopenia
• Risk of septicemia
– Intravenous immunoglobin for patients with
antibody deficiency
– MORTALITY:100%(SINCE MOST PATIENT
DIE )

16. THANK YOU