Wiskott-Aldrich Syndrome Health Article

Definition

Wiskott-Aldrich syndrome (WAS) is a rare inherited disorder marked by a low level of blood platelets, eczema, recurrent infections, and a high risk of leukemia or lymph node tumors.

Description

Wiskott-Aldrich syndrome (WAS) was named for the two physicians who reported the disorder. In 1937, A. Wiskott, a physician working in Munich, described two affected boys of German ancestry who had repeated infections, a skin rash, and poor blood-clotting ability. Nearly twenty years later, R. A. Aldrich reported similar symptoms in members of an American family of Dutch ancestry.

WAS is inherited as an X-linked genetic disorder and thus only affects males. The gene responsible for WAS is located on the short arm of the X chromosome. Since males have only one X chromosome they only have one copy of the gene. If that copy carries the abnormal gene, they have WAS. In contrast, females have two X chromosomes. They have a normal copy of the gene on one chromosome even if an abnormal gene is on the other because the abnormal gene is very rare. The normal copy on one X chromosome is usually sufficient to prevent females from having WAS. However, women who have one abnormal copy of the WAS gene are designated as carriers. While they will not have WAS, they have a 50 percent risk of passing the gene to each of their sons who will have WAS. Carrier females also have a 50 percent risk of passing the defective copy of the gene to their daughters who also become carriers.

Researchers identified the gene for WAS in 1994 and pinpointed its location on the short arm of the X chromosome. As of 2000, over 100 different mutations had been found in the gene among WAS patients. The fact that there are many mutations explains some of the variability of symptoms among boys with WAS. However, even within the same family, affected individuals with the identical WAS gene mutation may have different degrees of severity of the disease. The mild form, X-linked thrombocytopenia, is also caused by mutations in this same gene.

Demographics

The WAS syndrome affects one in every 250,000 male children and occurs worldwide. In the year 2000, scientists estimated that about 500 Americans had WAS.

Causes and symptoms

The syndrome is caused by a defect (mutation) in a specific gene called the WAS gene that normally codes for the protein named Wiskott-Aldrich syndrome protein (WASP). This vital protein is a component of cells that are important in the body's defense against infection (lymphocytes). The same protein also functions in the cells that help prevent bleeding (platelets). A less severe form of the disease, X-linked thrombocytopenia, affects mainly the platelets.

Increased susceptibility to infections, eczema, and excessive bleeding and bruising are the hallmarks of WAS, although the symptoms can vary significantly from one patient to another. The immune system of patients with WAS produces too few B and T cells. B cells are the cells in the body that make antibodies. There are many types of T cells. Both B and T cells are needed to defend the body against infection. Because both types of cells are affected, WAS patients are subject to repeated infections from bacteria, fungi, and viruses. Ear infections, meningitis, and pneumonia are common in boys with WAS.

WAS patients also have abnormal platelets, the specialized blood cells that help to form blood clots and control bleeding. In WAS, the platelets are often too few (called thrombocytopenia) and too small. Some of the earliest symptoms of the syndrome may be noted during early infancy, including excessive bleeding after a circumcision, bloody diarrhea, and a tendency to bruise very easily.

Some patients also have too few red blood cells (anemia) and an enlarged spleen (splenomegaly). About 10 percent of patients develop malignancies, usually leukemia or tumors in the lymph nodes (non-Hodgkin's lymphoma).

Diagnosis

The diagnosis of WAS is usually suspected in male infants who have excessive bleeding, eczema, and frequent bacterial or viral infections. Special blood tests can then be ordered to confirm WAS. The blood of Wiskott-Aldrich patients shows a low platelet count and a weak immune (antibody) response. Blood is analyzed to determine the quantity of immunoglobulins in the blood as well as the ability of the immune system to mount an antibody response against common pathogens. It is also possible to confirm the diagnosis by obtaining a small sample of the patient's blood and analyzing the DNA for a mutation in the WAS gene. Information about the exact mutation and the quantity of WAS protein the defective gene can produce may help predict the severity of the individual's condition.