Wiskott-Aldrich Syndrome

Etiology and pathogenesis

The disease is caused by a mutation in the WASP gene, which is located on the X chromosome. This gene encodes a specific WASP protein required for the normal functioning of blood cells.

A key feature of the syndrome is the development of microthrombocytopenia. Platelets are abnormally small, and their aggregation (clumping) ability is sharply impaired. At the same time, the bone marrow functions normally: the number of megakaryocytes in the myelogram remains within normal limits and they are morphologically unchanged. This proves that the problem lies not in impaired production of blood platelets, but in the presence of a qualitative defect in the platelets themselves and their subsequent accelerated destruction in the periphery. Morphologically, the thymus in this disease also remains unchanged.

Clinical Forms

Depending on the severity of the genetic defect, two main variants of the course are distinguished:

1. Classical form (Wiskott–Aldrich syndrome). Characterized by a full-blown and severe clinical picture. Includes the classical triad:
2. Hemorrhagic syndrome: caused by microthrombocytopenia.
3. Pronounced immunodeficiency: high susceptibility to recurrent bacterial, viral, and fungal infections.
4. Severe skin manifestations: atopic dermatitis, eczema.
5. X-linked thrombocytopenia. This is a milder, "mild/attenuated" variant of the disease. The main manifestation is increased bleeding. Pronounced immunodeficiency and severe eczema are not observed in such patients.

Diagnosis and differentiation of hemorrhagic syndrome

To verify Wiskott–Aldrich syndrome, an integrated approach is necessary:

• Myelogram (bone marrow examination): confirms a normal number and unchanged morphology of megakaryocytes.
• Molecular genetic methods: analysis of specific protein expression and direct search for mutations in the WASP gene.

In clinical differential diagnosis of hemorrhagic syndrome, Wiskott–Aldrich syndrome belongs to conditions with a microcirculatory (platelet) type of bleeding. It is characterized by:

• Asymmetric, painless ecchymoses (bruises).
• Absence of hemarthrosis (joint hemorrhages), which is typical for coagulopathies (e.g., hemophilia).
• Absence of elevated symmetric maculopapular rash characteristic of the vasculitic-purpuric type.

Laboratory findings in thrombocytopenias show increased bleeding time and positive endothelial tests (tourniquet, pinch tests), while aPTT and coagulogram remain normal (unlike in coagulopathies).

Class and exam questions

What else to study on this topic

• Classification of thrombocytopathies by platelet size (macro-, micro-, and normocytopenia).
• Differential diagnosis of microcirculatory, hematomal, and vasculitic-purpuric types of bleeding.
• Immune thrombocytopenia (ITP): clinical picture and criteria for distinction from hereditary defects.
• Common variable immunodeficiency (CVID) and mechanisms of humoral immunodeficiency.
• Glanzmann thrombasthenia and Bernard–Soulier syndrome as examples of other hereditary platelet defects.

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.