ConditionBlood & immune system
Wiskott-Aldrich Syndrome
Wiskott-Aldrich syndrome (WAS) is a rare inherited disorder of the immune system and platelets caused by changes in the WAS gene on the X chromosome, so it almost always affects boys. The classic signs are a low count of unusually small platelets (causing easy bruising and bleeding), eczema, and frequent infections, usually appearing in infancy. People with WAS also have a higher risk of autoimmune diseases and lymphoma. Stem cell transplant or gene therapy can cure it, and early treatment improves outcomes.
Also called: WAS, eczema-thrombocytopenia-immunodeficiency syndrome, X-linked thrombocytopenia (milder form)
At a glance
- What it is
- An X-linked primary immunodeficiency with low, small platelets.
- Who gets it
- Almost always boys; about 1 to 10 per million males.
- Classic triad
- Thrombocytopenia with small platelets, eczema, and recurrent infections.
- Other risks
- Autoimmune diseases (anemia, arthritis, vasculitis, kidney disease) and lymphoma.
- Diagnosis
- Blood count with small platelet volume, WAS protein testing, genetic testing.
- Treatment
- Stem cell transplant or gene therapy (curative), plus infection prevention, immunoglobulin and bleeding care.
When to get help
Call 911 or go to the ER
- Severe headache, vomiting, drowsiness or seizures in a child with WAS (possible bleeding in the brain), especially after a head injury
- Heavy bleeding that will not stop, vomiting blood or large amounts of blood in stool
- Fever of 38 °C (100.4 °F) or higher in a child with WAS who is unwell, or after a splenectomy
See a doctor within a day or two
- Any fever in a child with WAS
- New widespread bruising, tiny red skin spots, or nosebleeds lasting more than 10 minutes
- Bloody diarrhea in an infant
- Swollen glands, weight loss or night sweats
Book a routine appointment
- A baby boy with easy bruising, bloody stools, eczema and frequent ear or chest infections
- A family history of WAS or X-linked thrombocytopenia, before or during pregnancy
- Persistent eczema with frequent skin infections
What causes Wiskott-Aldrich syndrome
The WAS gene makes the Wiskott-Aldrich syndrome protein (WASp), which is found in blood cells. It helps cells change shape, move and communicate. When WASp is missing or faulty:
- Platelets are small, few and work poorly
- T cells, B cells and other immune cells do not function properly, so infections are frequent and the immune system can attack the body
Inheritance
The WAS gene is on the X chromosome. Boys have one X chromosome, so one faulty copy causes disease. Mothers who carry a faulty copy usually have no symptoms, and each son has a 50% chance of being affected and each daughter a 50% chance of being a carrier. Some cases are new changes with no family history.
Spectrum of disease
| Form | Features |
|---|---|
| Classic WAS | Small platelets, eczema, severe infections, autoimmunity, cancer risk |
| X-linked thrombocytopenia (XLT) | Mainly low, small platelets with mild or no immune problems |
| X-linked neutropenia | Rare; low neutrophils from a different type of WAS mutation |
Symptoms
Bleeding
- Easy bruising and tiny red or purple skin spots (petechiae)
- Bloody diarrhea, often an early sign in infants
- Nosebleeds and bleeding gums
- Prolonged bleeding after circumcision or minor cuts
- Bleeding in the brain, the most serious risk
Eczema
Itchy, inflamed skin often appears in the first year and can be severe and prone to infection. See eczema.
Infections
- Ear infections, sinusitis, pneumonia
- Skin infections
- Severe viral infections such as herpes and molluscum
- Infections with unusual organisms
Autoimmunity
Up to 40 to 70% of people with classic WAS develop autoimmune problems, including autoimmune hemolytic anemia, immune destruction of platelets, arthritis, vasculitis, inflammatory bowel disease and kidney disease.
Cancer
The risk of lymphoma, especially Epstein-Barr virus-associated B-cell lymphoma, is significantly increased, usually in adolescence or adulthood.
Diagnosis
- Complete blood count: low platelets with a characteristically small mean platelet volume on the blood smear, which distinguishes WAS from most other causes of low platelets such as immune thrombocytopenia.
- Flow cytometry to measure WASp in blood cells.
- Genetic testing of the WAS gene, which confirms the diagnosis and allows carrier testing and prenatal diagnosis.
- Immune tests: antibody levels, vaccine responses, lymphocyte counts.
Treatment
Curative treatment
- Hematopoietic stem cell transplant (HSCT): replaces the faulty blood and immune system with healthy donor cells. Outcomes are best when done early, ideally before age 5, with a well-matched donor.
- Gene therapy: the child's own stem cells are corrected with a working WAS gene and returned to them. It is available in specialist centers and clinical trials and avoids the need for a donor.
Supportive care
- Immunoglobulin replacement (IV or under the skin) to prevent infections
- Preventive antibiotics and antivirals in some cases
- Platelet transfusions for serious bleeding or before surgery
- Avoiding aspirin and NSAIDs and contact sports, and using a soft toothbrush
- Eczema care: emollients, topical steroids and treatment of skin infections
- Vaccinations: inactivated vaccines as advised; live vaccines are usually avoided
- Treatment of autoimmune problems with steroids or other immune medicines
- Splenectomy occasionally, to raise platelet counts in XLT, but it increases serious infection risk and requires lifelong precautions
Outlook
Without curative treatment, classic WAS causes serious complications, and life expectancy is reduced. After successful stem cell transplant or gene therapy, many children live healthy lives with normal platelets and immunity. Milder XLT has a better outlook but still carries risks of bleeding, autoimmunity and cancer, so long-term specialist follow-up is needed.
Frequently asked questions
What is Wiskott-Aldrich syndrome?
It is a rare inherited immune disorder caused by changes in the WAS gene on the X chromosome. It mainly affects boys and causes low, small platelets with bleeding, eczema, frequent infections, and increased risks of autoimmune disease and lymphoma.
What are the first signs of Wiskott-Aldrich syndrome?
Early signs in baby boys include easy bruising, tiny red skin spots, bloody diarrhea, prolonged bleeding after circumcision, eczema and repeated ear or chest infections. Symptoms usually appear in the first months of life.
How is Wiskott-Aldrich syndrome inherited?
It is X-linked recessive. Carrier mothers are usually healthy, and each son has a 50% chance of having the condition while each daughter has a 50% chance of being a carrier. Some cases arise from new gene changes.
Can Wiskott-Aldrich syndrome be cured?
Yes. Hematopoietic stem cell transplant can cure it by replacing the immune system, with best results when done early. Gene therapy using the child's own corrected stem cells is another curative option available at specialist centers.
How is Wiskott-Aldrich syndrome different from ITP?
Both cause low platelets, but in WAS the platelets are unusually small, and there are also eczema, infections and a family pattern affecting boys. In immune thrombocytopenia, platelets are normal or large in size and the immune system is otherwise normal.
Sources
This guide was written from current patient and clinical guidance, including:
- MedlinePlus Genetics: Wiskott-Aldrich syndrome
- Immune Deficiency Foundation: Wiskott-Aldrich syndrome
- NIAID: Wiskott-Aldrich Syndrome
- GeneReviews (NCBI): WAS-Related Disorders
- NIH Genetic and Rare Diseases Information Center: Wiskott-Aldrich syndrome