THE WISKOTT-ALDRICH SYNDROME: A GENETIC DEFECT FUNCTIONALLY EXPRESSED IN MARROW STEM CELL DERIATIVES

Abstract

Three of four non-related boys presented with thrombocytopenia, eczema, bloody diarrhea and frequent infections. The fourth initially had thrombocytopenia only, was splenectomized, and subsequently developed repeated infections and eczema. Immunoglobulins were variably abnormal. Antibody production to bacteriophage OX 174 (a protein antigen) was abnormal with low primary and severely impaired secondary response. No IgG antibody was formed. Lymphocyte transformation with non-specific mitogens and allogeneic cells was significantly impaired and the number of E-rosettes diminished. Volumetric size of platelets was reduced to 50%. Except in the splenectomized patient, autologous platelet survival time was normal. In all patients, in vivo and in vitro platelet function when corrected for platelet size was normal. Since megakaryocyte mass was adequate, thrombocytopenia must result from ineffective thrombocytopoesis. Red blood cell (RBC) size was also reduced. The abnormal B and T-cell function, the ineffective platelet production and decreased size of platelets and RBC in this X-linked disease suggests that a single genetic defect is expressed functionally in all stem cell derivatives.