Disease Information
Inherited Immunodeficiencies: Wiskott-Aldrich Syndrome (WAS)
Alternative Names: WAS
Definition
Wiskott-Aldrich syndrome (WAS) is an inherited disorder of the immune system that affects males but not females. It is characterized by recurrent infections, low numbers of circulating blood platelet cells (thrombocytes) and eczema (skin rash). The disorder is caused by a mutation (mistake) in the WASP (Wiskott-Aldrich syndrome protein) gene.
The mistake results in defective functioning of T cells, B cells and platelets. In the normal individual the T cells are responsible for providing protection against certain viral and fungal infections. B cells are precursors to antibody producing cells.
Platelets (thrombocytes) are the cells responsible for blood clotting. The most characteristic feature of WAS is a low platelet count with small platelets. As a result of the gene defect, males have an increased susceptibility to infections and bleeding. The diagnosis is confirmed by mutation detection (looking for a mistake in the WAS gene).
Incidence
Wiskott-Aldrich syndrome occurs with a frequency of about 4/ million.
Influencing Factors
Pattern of inheritanceThe gene for Wiskott-Aldrich syndrome is found on the X chromosome. Because females have two X chromosomes, if they have a mutation on one X chromosome, they have a spare X that can help compensate for the mutation. Males have one X chromosome and one Y chromosome. Since they do not have a spare X chromosome, they show signs of a mutation inherited on the X chromosome. Although, a female who carries a mutation for Wiskott-Aldrich syndrome on one of her X chromosomes, shows no sign of immunodeficiency, her sons and daughters have a 50 percent chance of inheriting the X chromosome with the mutation (and a 50 percent chance of inheriting the normal X chromosome). The sons who inherit the mutant X chromosome will have WAS and the daughters who inherit the mutant X chromosome will be carriers like their mother. Carriers of WAS can be identified by mutation detection (a laboratory test).
All of the daughters of a man with Wiskott-Aldrich syndrome will be carriers of WAS; but the sons, who have inherited his unaffected Y chromosome, will be normal. About 50 percent of patients with Wiskott-Aldrich syndrome will have a brother, cousin or uncle with WAS. In most remaining families, the affected individual represents the first sign of a new mutation (mistake) in the WAS gene in his family. We do not know what causes new mutations in most families.
Typically, the disorder affects males, but there have been some females who appear to have the same physical problems as males with WAS, without the genetic mutation (mistake).
Clinical Features and Symptoms
The diagnosis of Wiskott-Aldrich syndrome is suspected in males who have bleeding in the newborn period. This is most often manifested as bloody diarrhea. Other patients are recognized to have WAS when a blood count (CBC) that is done during an infection, shows a low platelet count with small platelets.
Because of the defect in T cells and B cells, patients with WAS are at increased risk for both bacterial and viral infections. Otitis (ear infections), sinusitis and pneumonia are frequently seen in patients with Wiskott-Aldrich syndrome. Viral infections caused by herpes simplex and EBV (Epstein-Barr Virus) can also be troublesome.
Autoimmune disorders, caused by an abnormal immune system, can also be observed in males with WAS. These include vasculitis, arthritis, and autoimmune hemolytic anemia.
An increased incidence of malignancy has also been observed in patients with WAS. Specifically, EBV-related brain tumors, leukemias and lymphomas are seen.
Survival Rates
The prognosis for males diagnosed with Wiskott-Aldrich syndrome has improved due to antibiotic therapy, intravenous gammaglobulin (IVIG) and bone marrow transplantation. However, because T cell function declines over time, WAS is considered a progressive disorder and without bone marrow transplant males usually die in their early twenties from an overwhelming infection or a malignancy.
Males with Wiskott-Aldrich syndrome are encouraged to lead as normal a life as possible, which includes good health habits.
Treatment Strategies
At St. Jude, males with Wiskott-Aldrich syndrome are treated with monthly infusions of gamma globulin (IVIG), chronic prophylactic antibiotics, and vigorous skin care for the eczema. Some patients are also given anti-viral medicines for herpes simplex prevention. At some centers, patients are treated with splenectomy to improve the platelet count.
At this time, bone marrow transplant is the only cure. Family members (siblings and parents) can have a blood test to see if they are a suitable donor (match) for the affected male for a bone marrow transplant. If no family member is a match, a matched unrelated donor may be used.
Current Research
• Better understanding the role of the WASP gene in the normal hematopoietic system• Continually improving transplant regimens to cure Wiskott-Aldrich syndrome• Investigating the use of gene therapy to cure WAS
*Information provided by St. Jude*
