Wiscott-Aldrich Syndrome

1. Thrombocytopenia (bleeding)
2. Infections
3. Eczema

What are the genetics?
What do the platelets look like?
What is the defect?
What are the usual presenting sx in infancy?

Wiscott-Aldritch

• Problem: results from mutations in WASP (intracellular signaling molecule involved in T cell receptor signaling)
• X-linked recessive disorder (X chrom p11.22-23)
• triad
  • recurrent infections
    • defects in humoral and cell-mediated immunity, esp IgM deficiency
    • causing recurrent sinopulmonary infections (PNA, OM) with encapsulated organisms (S. pneumoniae, H. influenzae), in the first year of life
    • opportunistic infections with P. jiroveci, recurrent HSV (later)
    • sepsis or meningitis due to encapsulated orgs, or opportunistic orgs.
  • bleeding (due to thrombocytopenia)
    • platelet counts in the range of 15 to 30 x 10^3/ mm3
    • small platelets (think of Scott, a small asian, vs a big St. bernard (bernard soulier - large platelets)
    • prolonged bleeding from circumcision site, or bloody diarrhea during infancy (usual presenting symptoms)
    • at times, may be life-threatening (eg, intracranial hemorrhage).
  • eczema - often seen before 6 mos of age; cutaneous findings are typical of atopic dermatitis, although petechiae may be observed.
• Long term px (death by 6-11 years)
  • Infections common cause of death
  • Hemorrhage is a common cause of death
  • Autoimmune cytopenias
  • Vasculitis
  • Increased risk of lymphoma and leukemia
  • #1 cause of death= EBV-induced lymphoma
• Labs: Decreased T cell numbers (CD3+, CD4+, CD8+) and function; low IgM
• Prenatal Dx: chorionicvillous sampling, amniocentesis
• Treatment: IVIG, BMT