Inheritance: X-linked recessive
Genetic defect: defect in the gene for the WAS protein (WASP), localized to the short arm of the X chromosome (Xp11.23)
Clinical features:
(1) Most affected patients are males, with onset typically during infancy.
(2) There is an immune deficiency with recurrent infections which may be fulminant.
(2a) There is a failure to produce antibodies to polysaccharide antigens and there is a poor response to vaccinations.
(2b) There is a combined defect in cell-mediated immunity affecting both B and T cells.
(2c) Patients may have recurrent respiratory tract infections, otitits and/or diarrhea.
(2d) Patients may have infections with opportunistic pathogens such as pneumocystis pneumonia.
(2e) Viral infections may be severe and patients may develop infections following vaccination with live-virus vaccines.
(3) Most patients develop eczema.
(4) Patients may have a moderate to severe bleeding disorder.
(5) Patients have a predisposition to immune disorders.
(5a) autoimmune hemolytic disease (AIHD)
(5b) immune thrombocytopenia (ITP)
(5c) immune complex disorders
(6) Patients have a predisposition to malignancies, especially leukemia and lymphoma.
Laboratory features:
(1) There is a moderate to severe thrombocytopenia.
(2) Platelets are very small in size, and there is a marked decrease in total platelet volume.
(3) The bleeding time is prolonged.
(4) Platelet function is impaired due to a platelet storage pool defect.
(5) IgM levels are reduced. IgG may be reduced to normal. IgA and IgE may be increased.
(6) ABO antibodies may be weak or absent.
(7) T cells show impaired function and reduce response to mitogens.
(8) Lymphocytopenia may develop as the patient gets older.
(9) There are reduced microvillous projections on the surface of T lymphocytes.
