Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Wiskott-Aldrich Syndrome (WAS) [D82.0]

OMIM numbers: 301000300392 (WAS)

Dr. rer. nat. Barbara Bangol, Dr. med. Imma Rost

Scientific Background

The Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency that affects both B and T lymphocytes and is characterized by the triad of thrombocytopenia, eczema and infections. A clinically less severe form is the X-linked thrombocytopenia (XLT). The incidence of 1-10 in 1,000,000 for WAS is probably underestimated. Already at birth, petechiae, hematomas and blood stools may occur. In later stages, 80% of all patients suffer from eczema that are similar to atopic dermatitis. Besides thrombocytopenia, the thrombocytes are smaller than usual and exhibit a decrease in aggregation ability. In approximately 30% of all cases, life-threatening hemorrhages may occur. Bacterial infections such as otitis media, sinusitis, pneumonia, sepsis and meningitis as well as severe, sometimes recurring virus infections such as herpes simplex, occur frequently. Approximately 40% of all patients suffer from autoimmune diseases such as hemolytic anemia, polyarthritis, inflammatory bowel diseases and IgA nephritis. More than 10% of all patients develop malignomas, especially EBV-associated B cell lymphomas. Blood tests show thrombocytopenia with small platelets with impaired aggregation, abnormal B and T cell functioning as well as abnormal immunoglobulines and antibody tests. Lymphopenia develops with advancing age. Therapy of choice is blood stem cell transplantation or symptomatic treatment with antibiotics, immunoglobulines and, if required, thrombocyte concentrates.

The disease is caused by mutations in the WAS gene, which plays a role in the organisation of the actin cytoskeleton, the signal transduction, phagocytosis and apoptosis. Mutations are located all over the entire gene; however, 45% of all mutations are found in the domain P4/WH1. Mutations which inhibit the WAS expression entirely have been associated with WAS; partially inactivating mutations lead to XLT. Female carriers show a non-random X inactivation.