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Wiskott-Aldrich Syndrome

What is Wiskott-Aldrich syndrome (WAS)?

Wiskott-Aldrich syndrome (WAS) is a serious medical condition that causes problems both with the immune system and with blood clotting. Patients with WAS may be very susceptible to infections caused by bacterial and fungal organisms. Many patients also have a moderate to severe eczema (red, scaly skin rash). Finally, patients with WAS can experience easy bruising and bleeding. This is because people with WAS have low numbers of small, non-functional platelets, the cells in the blood that clump together to form blood clots.

Children with WAS are diagnosed most commonly in the first 1-2 years of life because of easy bruising, abnormal bleeding, or low platelet counts. Patients may also have severe or frequent infections, including bacterial ear infections, sinus infections, pneumonia, blood infections, or viral infections.

Patients show a wide variation in the severity of the disease Four types have been identified:

  1. Classic or Severe WAS: This is the most severe form of WAS.
  2. X-Linked Thrombocytopenia (XLT): This is milder form of WAS where the platelets are affected but there is little or no immunodeficiency. Sometimes the symptoms of WAS and XLT overlap, making the distinction between the two unclear.
  3. Intermittent Thrombocytopenia: The mildest form called where the platelet abnormalities are intermittent and there is no immunodeficiency.
  4. X Linked Neutropenia: This is the rarest form in which the platelets are normal but there is a serious defect in the neutrophils (a kind of white blood cell). Patients can have serious and recurrent infections.

Symptoms of WAS vary among patients. Individuals with classic WAS may have bleeding, frequent infections, eczema and often develop autoimmune disorders or malignancy. Individuals with XLT may have just bleeding manifestations or may have eczema. The symptoms typically present at birth or in infancy.

WAS is caused by a mutation in the WAS gene that is located on the X chromosome. The production of the WAS protein is controlled by the WAS gene. This gene instructs cells to make the WAS protein. When this gene is mutated, it results in patients having abnormal, reduced or absent protein causing WAS.

WAS is an X-linked disorder. In X-linked disorders, females may carry the gene for the disorder but don’t develop symptoms, whereas boys develop the clinical problems associated with the disease. WAS is estimated to occur in approximately one out of every 100,000 boys. For more information click here.

The diagnosis of WAS should be considered in any boy with unusually increased bruising or bleeding, particularly if it was noticed soon after birth or in infancy. Additional criteria include recurrent bacterial, viral infections in infancy and early childhood, eczema, the presence of autoimmune disorders or lymphoma. There may be a family history of similar symptoms among brothers, cousins or maternal uncles.

Once the diagnosis of WAS is clinically considered, the following laboratory tests may be ordered:

  • Complete Blood Counts (CBC with differential) – This test includes the count and size of platelets. WAS patients present with platelet size that is significantly smaller than normal.
  • Immunoglobulin levels (IgG, IgM, IgA, IgE) – Immunoglobulins (antibodies) levels in blood may be low in WAS
  • Specific antibody titers - These tests may detect decreased antibody response to vaccines, in particular to the Pneumovax, and low levels of antibodies to red cells (isohemagglutinins) normally present in all people
  • WAS protein levels in white blood cells - Absent, decreased or abnormal intracellular WASP in the white blood cells is also used as a screening tool for early diagnosis of WAS.
  • Specific genetic testing - Confirmation of the diagnosis of WAS is done by testing for mutations in the WASP gene on the X chromosome.

When a boy has been diagnosed with WAS, there are several possible treatment options. Physicians and parents choose different treatment options according to the severity of the diseases. Physicians review individual cases and make recommendations on the treatment options that are most suitable

Treatment for WAS may include the following:

  • Medications – especially antibiotic, antifungal, and antiviral medications to treat or prevent active infections
  • Avoiding exposure to infections, especially ones that may be difficult to eradicate, such as chicken pox.
  • Using a helmet to reduce the risk of head trauma and intracranial hemorrhage
  • Avoid nonsteroidal anti-inflammatories such as Ibuprofen (Motrin, Advil) or Aspirin (ASA) that can further impair platelet function.
  • Use immunoglobulin supplementation (IVIg) when specific antibody responses are not developed
  • A blood and marrow transplantation is the only proven cure for WAS. Other measures primarily provide relief from symptoms and decrease the risk of infections. Many physicians recommend that patients with Classic WAS undergo a transplant as early as possible. Transplant has the best success rate if it is done early in life with a well-matched donor.
  • Research clinical trials involving gene therapy for WAS may be available. Discuss with your doctor to determine if this is something you / your child may be eligible for. At this time, gene therapy for WAS is considered experimental and not a standard treatment.
  • The management of patients with XLT is less clear and the decision to transplant or not is debated by the experts. Currently, some patients with XLT undergo a transplant whereas others opt for more conservative treatment.

Frequently Asked Questions

The lower platelet count predisposes the patient to spontaneous bleeding and prolonged, severe bleeding with injuries. Care should be taken to prevent injuries as much as possible. A helmet is recommended for infants and children when they becoming are actively mobile. Contact sports should be avoided, and the activities of the individual patient are best determined by the physician and the parents. A medical alert bracelet indicating that the patient has low platelets is recommended, as this can help patients receive prompt and appropriate care.

There are a few ways in which the platelet counts can be increased:

  • Transfusions: A platelet transfusion can increase the platelet counts for several days. Platelet transfusion can be used to control moderate to severe bleeding. It is also used to control a bleed that is not/cannot be controlled by other methods. Platelet transfusion may be used prior to surgery to improve the counts and prevent excessive bleeding during the surgery and during the recovery period. In general, it is better to keep platelet transfusions to a minimum and use other means to control the bleeding if possible.
  • High dose IVIG: Platelet counts may increase is some patients who are given high doses of IVIG. If there is significant improvement, IVIG is given every three to four weeks to keep the platelet counts up.
  • Medications: Patients with WAS can develop immune mediated thrombocytopenia (ITP, where thrombocytopenia means low platelets) where their immune system destroys their own platelets. Medications that are used for these patients include steroids such as prednisone, high dose IVIG and rituximab. These can help control the immune reaction and increase the platelet counts.