« Understanding Primary Immunodeficiency (PI)

Types of PI

Primary immunodeficiency (PI) diseases are characterized in many different ways, including:

  • Low antibody levels
  • Defects in antibodies
  • Defects in the cells and proteins of the immune system (for example, T cells, B cells, neutrophils, or the complement system)

These defects make people susceptible to recurrent infections, and other complications that may require different therapies. The most common primary immunodeficiency types result in an inability to make a very important type of protein called antibodies or immunoglobulins, which help the body fight off infections from bacteria or viruses. In addition to increased susceptibility to infection, people with PI may also have autoimmune diseases in which the immune system attacks their own cells or tissues.

PI Type:

Wiskott-Aldrich Syndrome (WAS)

Definition of WAS

Wiskott-Aldrich syndrome is a PI disease that affects both the T and B lymphocytes. In addition, the platelets—blood cells that help control bleeding—are reduced in number and size. People with WAS experience frequent bacterial, viral, and fungal infections; eczema of the skin; and an increased tendency to bleed.

WAS is caused by mutations—or mistakes—in the gene that produces a protein named for the disorder, the Wiskott-Aldrich Syndrome Protein (WASP), which is located on the X chromosome. Because the gene defect is carried on the X chromosome (X-linked recessive), only boys can inherit WAS.

People with WAS demonstrate a classic pattern of symptoms:

  • Increased tendency to bleed, caused by a significantly reduced number of platelets
  • Recurring bacterial, viral, and fungal infections
  • Eczema of the skin

Symptoms of WAS

Individuals with WAS can develop different symptoms. Some people have all three classic symptoms; including: low platelets, immunodeficiency, and eczema while others experience only low platelet counts and bleeding. All are related to the mutation of the WAS gene.

  • Bleeding: A reduction in the size and number of platelets is a hallmark of WAS. These small platelets are unique to WAS, and their presence is useful in making a diagnosis. Bleeding into the skin may cause bluish-red spots (called petechiae) ranging in size from small pinheads to large bruises. Boys with WAS may also experience bloody bowel movements (especially in infancy), bleeding gums, and prolonged nose bleeds. Bleeding into the brain is a particularly dangerous complication.
  • Infections: Ear infections, sinus infections and pneumonia are common in WAS due to the deficiency of both B and T lymphocyte function. More severe infections of the bloodstream may also occur, as well as meningitis or severe viral infections.
  • Eczema: People with classic WAS frequently suffer from eczema. In infants, the eczema may resemble “cradle cap” or severe diaper rash; in older boys, it may be limited to the skin creases around the front of the elbow, around the wrist and neck, and behind the knee.
  • Autoimmune manifestations: A high incidence of “autoimmune-like” (conditions that result from the unhealthy immune system attacking the patient's own body) symptoms are common in both infants and adults with WAS. The most common of these are vasculitis, an inflammation of the blood vessels; hemolytic anemia, where the body destroys its own blood cells; and idiopathic thrombocytopenia purpura (ITP), where the immune system attacks the platelets.
  • Malignancies: Cancer can occur more frequently in patients with WAS. Most of these cancers, such as lymphoma or leukemia, involve the B cells.

Diagnosis of WAS

Because the platelet abnormalities of WAS are almost always present even in the cord blood at birth, the simplest way to diagnose WAS is to obtain a platelet count and determine the platelet size. WAS platelets are significantly smaller than normal platelets. In children over the age of 2, the frequency of infections and deficiencies in the immune system can be used to support the diagnosis.

The diagnosis is confirmed by demonstrating an absence of the WAS protein in blood cells, or by the identification of a mutation within the WAS gene.

Wiskott Aldrich Syndrome protein Wiskott Aldrich Syndrome protein

Treating WAS

Only your doctor can determine which treatment is right for you and your specific health needs. Visit our Treating PI section to read about the types of PI treatment and download questions to ask your doctor.