Wiskott–Aldrich syndrome

Immunodeficiency with thrombocytopenia and eczema

The Wiskott -Aldrich syndrome (WAS) is an X - linked recessive disorder with impairment of blood clotting and the immune system, characteristically in the triad of eczema (skin rash), thrombocytopenia expresses ( lack of platelets) and recurrent infections. The incidence of male live births is approximately 1:100,000 to 1:250,000. The life expectancy is not more than ten years in general.

The syndrome is named after the German pediatrician Alfred Wiskott (1898-1978) and the American Robert Anderson Aldrich ( 1917-1998 ).

Cause

Mutations in the so-called Wiskott -Aldrich syndrome gene (abbr. WAS gene locus Xp11.23 - p11.22 ) lead to impairment of cellular signal transduction. The Aktinbildung is limited, which makes the formation of platelets is reduced from the megakaryocytes.

Symptoms

Occur shortly after birth as a result of neonatal thrombocytopenia first punctiform ( petechial ) haemorrhages, gastrointestinal and intracranial bleeding will be added in later years. This typical of atopic dermatitis -like dermatitis also developed in the first days of life.

While the T- cell immunity at the beginning is still normal, humoral immunity is significantly reduced in the first year of life. The T- cell immunity takes in the years to decrease continuously, so that the tendency to infection rises sharply. In the second year of life first appear on recurrent, opportunistic infections such as pneumonia, otitis, septicemia and meningitis. Common pathogens are pneumococci, Haemophilus influenzae, meningococcal, and Pneumocystis jirovecii.

Often the young patients also suffer from autoimmune diseases such as vasculitis, arthritis, and hemolytic anemia. Malignancies of the lymphoreticular system can be found frequently in Wiskott- Aldrich patients.

Diagnostics

The following characteristic changes raise the suspicion of a Wiskott -Aldrich syndrome:

• The IgM antibodies are lowered, the IgG antibodies in normal mode, IgA, IgD and IgE increased above the norm.
• In the blood there is typically a high degree of thrombocytopenia with small platelets ( mean platelet volume = low MPV).
• The Impfantikörper are reduced.
• After the age of six first appear on heavy lymphopenias.

In this disease, the Wiskott -Aldrich protein ( WASP ) is not expressed correctly. WASP is required for the organization of the cytoskeleton. If there is no protein in the hematopoietic stem cells, T and B lymphocytes, macrophages, dendritic cells, NK cells, and platelets are not fully functional. It may be determined to confirm the diagnosis.

The diagnosis is confirmed by molecular genetic analysis by mutational analysis. Prenatal diagnosis is also possible.

Therapy

Causal therapy

Through a stem cell transplant to restore a functioning immune system can attained werden.Gentherapeutische measures are used in the context of controlled clinical trials. A first clinical trial was initiated at the Hannover Medical School in 2006. Initial results show that transplantation of retrovirally modified stem cells may cure the disease. The safety and sustained efficacy is currently under review.

Symptomatic therapy

These patients must be treated consistently early antibiotic at the first sign of infection. Cotrimoxazole is for Pneumocystis prophylaxis, penicillin V used for pneumococcal prophylaxis. The lack of immunoglobulins can be substituted. Should serious bleeding platelet concentrates are transfused.