Makindo Medical Notes

Related Subjects: |X linked Agammaglobulinaemia (Bruton) |X-linked lymphoproliferative disease (Children) |Chediak Higashi syndrome |Common variable immunodeficiency |Severe combined immunodeficiency disorders |DiGeorge syndrome (thymic aplasia) |Selective IgA deficiency |Wiskott-Aldrich syndrome (Children) |T lymphocytes

Consider Wiskott-Aldrich syndrome if a child presents with eczema, low platelets, and recurring infections.

About

• Wiskott-Aldrich Syndrome (WAS) is a rare, X-linked recessive disorder primarily affecting boys.
• The condition is characterized by defective platelets, leading to an increased risk of bleeding, infections, and haematological malignancies.
• It almost exclusively affects male children due to its X-linked inheritance pattern.

Aetiology

• WAS is caused by mutations in the gene on the X chromosome that codes for the Wiskott-Aldrich Syndrome Protein (WASP).
• WASP is a cytoplasmic protein involved in the regulation of actin polymerization, which is essential for proper immune cell function.
• Mutations lead to defective cytoskeleton function, impairing cell shape changes after activation and cell motility, especially in immune cells.

Clinical Features

• Presents in male children with severe eczema, which may be difficult to control.
• Thrombocytopenia (low platelets) often results in bleeding symptoms, such as bloody diarrhoea or easy bruising.
• Recurrent bacterial, viral, and fungal infections due to immunodeficiency.
• There is an increased risk of developing haematological malignancies (e.g., lymphoma).

Investigations

• Immunoglobulin levels can vary, but typically there is low IgM and normal IgG.
• Lymphopenia and a reduced number of CD8+ T cells are seen in some cases.
• Prenatal diagnosis can be made via chorionic villus sampling (CVS) or amniocentesis to detect the genetic mutation.

Management

• The best treatment is HLA-identical sibling bone marrow transplantation to restore immune function.
• Splenectomy may be considered to improve platelet counts in cases of severe thrombocytopenia.
• Intravenous immunoglobulin (IVIg) may be required to boost immune function and reduce infections.