Published: 18 Jun 2025

ICD9: 279.12      ICD10: D82.0      ICD11: 3B62.0Y

Wiskott-Aldrich syndrome (WAS) is a rare, inherited immunodeficiency disorder that primarily affects males.
It's characterized by a triad of symptoms:

Thrombocytopenia: Low platelet count, leading to easy bruising, prolonged bleeding, and sometimes internal hemorrhages. The platelets are also typically smaller than normal.

Eczema: A chronic, itchy, red, and inflamed skin condition that can be severe and difficult to manage.

Immunodeficiency: A weakened immune system, making individuals susceptible to recurrent infections, particularly those caused by bacteria, viruses, and fungi.

Here's a more detailed breakdown:

Genetics: WAS is caused by mutations in the *WAS* gene located on the X chromosome. This gene provides instructions for making a protein called WASP (Wiskott-Aldrich Syndrome Protein). WASP is crucial for the proper function of blood cells, particularly those involved in the immune response and blood clotting. Because it's X-linked, males are more commonly affected (they have one X chromosome), while females are usually carriers (they have two X chromosomes, so one normal copy can compensate). However, some females can also experience milder symptoms.

Mechanism: The *WAS* gene mutation leads to a dysfunctional or absent WASP protein. WASP plays a critical role in:
Cytoskeleton organization: It helps regulate the cytoskeleton of blood cells, which is essential for cell movement, signaling, and proper function.
Immune cell function: WASP is vital for T cell activation, B cell function, and the ability of immune cells to migrate to sites of infection.
Platelet production and function: WASP contributes to the formation and normal function of platelets.

Symptoms:
Bleeding: This is often the first symptom noticed, appearing in infancy or early childhood. It can manifest as:
Bruising easily
Prolonged bleeding from minor cuts or injuries
Nosebleeds
Bleeding gums
Blood in the stool or urine
More severe internal bleeding
Eczema: Typically develops early in life and can be widespread and severe. It's often resistant to typical treatments.
Infections: Recurrent and often severe infections are common due to the weakened immune system. These can include:
Ear infections
Pneumonia
Sinus infections
Skin infections
Meningitis
Autoimmunity: Individuals with WAS have an increased risk of developing autoimmune disorders, where the immune system attacks the body's own tissues. Examples include:
Autoimmune hemolytic anemia (destruction of red blood cells)
Vasculitis (inflammation of blood vessels)
Inflammatory bowel disease
Increased risk of cancer: People with WAS have a higher risk of developing certain types of cancer, especially lymphomas and leukemia.

Diagnosis: Diagnosis usually involves a combination of:
Clinical evaluation: Assessment of symptoms and medical history.
Blood tests:
Complete blood count (CBC) to check platelet count and other blood cell levels.
Immunoglobulin levels to assess immune function.
Flow cytometry to assess WASP expression in immune cells.
Genetic testing: To identify mutations in the *WAS* gene.

Treatment: Treatment options depend on the severity of the condition and can include:
Supportive care:
Antibiotics to treat infections
Topical corticosteroids and emollients for eczema
Platelet transfusions to manage bleeding
Intravenous immunoglobulin (IVIG) to boost the immune system.
Hematopoietic stem cell transplantation (HSCT): This is currently the only curative treatment for WAS. It involves replacing the patient's defective bone marrow with healthy stem cells from a matched donor.
Gene therapy: This is an emerging treatment option where a functional copy of the *WAS* gene is introduced into the patient's blood cells. It shows promising results.
Splenectomy: Removal of the spleen may be considered in some cases to increase platelet counts, but it also increases the risk of infection.

Prognosis: The prognosis for individuals with WAS varies depending on the severity of the condition and the treatment they receive. Without treatment, the life expectancy is significantly reduced due to infections, bleeding, and autoimmune complications. HSCT and gene therapy can significantly improve the prognosis and offer the possibility of a normal lifespan.

It is important to remember that WAS is a complex disorder, and the information provided here is for general knowledge only. If you suspect that you or someone you know may have WAS, it is essential to consult with a qualified healthcare professional for diagnosis and treatment.