Conditions · Pediatrics and neonatology
Wiskott–Aldrich syndrome !
A rare inherited disorder of boys with eczema, small and few platelets that cause bleeding, and a weak immune system with frequent infections.
Updated 2026-11-01
Structures involved
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Why it happens
- Mendelian inheritance: autosomal dominant, recessive and X-linked
- Primary hemostasis and platelets
- Innate and adaptive immunity: overview
- Cytoskeleton: microfilaments, intermediate filaments, microtubules
What it is
An X-linked primary immunodeficiency caused by mutations in the WAS gene. Its classic triad is eczema, thrombocytopenia with small platelets (microthrombocytopenia) and recurrent infections, with a high risk of autoimmunity and lymphoma.
Who gets it
Very rare: about 1 to 10 per million males worldwide, almost always boys. Bleeding usually appears in the first months of life. In Latin America, as elsewhere, it is often first mistaken for immune thrombocytopenia.
Causes
- Mutations in the WAS gene on the X chromosome, which encodes the WAS protein (WASP)
- X-linked recessive inheritance; carrier mothers are usually healthy
- Milder variants of the same gene cause X-linked thrombocytopenia
Risk factors
- Male sex
- Family history of affected maternal male relatives
Pathophysiology
WASP regulates the actin cytoskeleton of blood cells. Without it, platelets are small and short-lived and are removed in the spleen, causing bleeding. T cells, B cells, NK cells and phagocytes move and signal poorly, so antibody responses to polysaccharide antigens fail (low IgM), predisposing to encapsulated bacteria, viruses and opportunistic organisms. Defective regulatory T cells explain eczema and autoimmunity, and impaired immune surveillance raises the lymphoma risk.
Classification
- Classic Wiskott–Aldrich syndrome (full triad)
- X-linked thrombocytopenia (mainly platelet disease, mild immune defect)
- X-linked neutropenia (activating WAS mutations)
Symptoms and signs
- Bleeding from early infancy: petechiae, bruising, bloody diarrhoea, prolonged bleeding after circumcision
- Eczema resembling atopic dermatitis, often severe
- Recurrent otitis media, sinusitis and pneumonia
- Infections by encapsulated bacteria, viruses (herpes) and Pneumocystis
- Autoimmune disease: haemolytic anaemia, vasculitis, arthritis, kidney disease
Diagnosis
- Clinical
- Suspected in a boy with early bleeding, eczema and recurrent infections, especially with a family history on the mother's side.
- Tests
- Complete blood count with low platelet count and low mean platelet volume (small platelets on the smear); immunoglobulins typically show low IgM, normal IgG, and high IgA and IgE; poor antibody response to polysaccharide vaccines. Flow cytometry for absent WASP and WAS gene sequencing confirm it.
- Imaging
- Not needed for diagnosis; brain CT if intracranial bleeding is suspected and imaging for lymphoma when suggested by symptoms.
Differential diagnosis
- Immune thrombocytopenia (large platelets, no eczema or immunodeficiency)
- Hyper-IgE syndrome (eczema and infections, normal platelets)
- Severe atopic dermatitis with secondary infections
- Other inherited thrombocytopenias
Goal of treatment
Prevent bleeding and infection, control eczema and autoimmunity, and offer curative cell therapy early.
Treatment
- Procedure
- Haematopoietic stem cell transplantation is the curative treatment, best done early in childhood; gene therapy is available in some centres.
- Medical
- Immunoglobulin replacement and antibiotic prophylaxis (including against Pneumocystis); topical therapy for eczema; immunosuppressants for autoimmune disease.
- Acute
- Platelet transfusion for serious bleeding, using irradiated, filtered blood products.
- Follow-up
- Bleeding precautions (no antiplatelet drugs or intramuscular injections, careful handling), infection surveillance, avoidance of live vaccines, and screening for lymphoma.
Complications
- Intracranial and gastrointestinal haemorrhage
- Severe and opportunistic infections
- Autoimmune haemolytic anaemia and vasculitis
- Lymphoma, often associated with Epstein–Barr virus
- Post-splenectomy sepsis
Prognosis
Without curative treatment, survival into adulthood is limited by bleeding, infection and lymphoma. Stem cell transplantation in early childhood, ideally from a matched donor, gives long-term survival in most children.
Prevention
- Genetic counselling and carrier testing of female relatives
- Prenatal diagnosis in families with a known mutation
Test yourself
Think of the answer, then tap the question to see it.
What is the classic triad of Wiskott–Aldrich syndrome?
Eczema, thrombocytopenia with small platelets, and recurrent infections.
Which platelet finding distinguishes it from immune thrombocytopenia?
Small platelets (low mean platelet volume); in immune thrombocytopenia they are normal or large.
What is the typical immunoglobulin pattern?
Low IgM, normal IgG, and raised IgA and IgE.
What is the inheritance pattern and the defective protein?
X-linked recessive; WASP, a regulator of the actin cytoskeleton.
What is the only curative treatment?
Haematopoietic stem cell transplantation (gene therapy in selected centres).
Related conditions
- Atopic dermatitis
- Immune thrombocytopenia (ITP)
- Non-Hodgkin lymphoma
- Autoimmune haemolytic anaemia
- Intracerebral haemorrhage
- X-linked (Bruton) agammaglobulinaemia
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Wiskott-Aldrich syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); About Primary Immunodeficiency (PI) (Centers for Disease Control and Prevention (CDC), 2026).
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