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
📖 About
- X-linked lymphoproliferative disease (XLP), also called Duncan disease, is a rare primary immunodeficiency that severely impairs the immune system’s response to viral infections, especially Epstein–Barr virus (EBV).
🧬 Aetiology
- Caused by mutations in the SLAM-associated protein (SAP) gene (SH2D1A).
- 🔗 SAP normally regulates SLAM (signalling lymphocyte activation molecule) on T and B cells.
- ❌ Loss of SAP → dysregulated T- and B-cell interactions → uncontrolled immune responses, particularly to EBV.
- 🩺 HSCT (bone marrow transplant) from an HLA-identical donor can restore normal immune function.
🩺 Clinical Features
- ⚠️ Extreme sensitivity to EBV infection.
- EBV exposure may trigger severe or fatal infectious mononucleosis with massive immune activation.
- Risk of lymphoproliferative disorders (uncontrolled lymphocyte growth) and immune dysregulation.
- 📉 May progress to haemophagocytic lymphohistiocytosis (HLH), bone marrow failure, or liver disease.
🔎 Investigations
- 🧪 Hypogammaglobulinemia (↓ IgG, IgA, IgM) due to impaired B-cell function.
- ⬆️ High risk of EBV-driven B-cell lymphomas, especially Burkitt lymphoma.
- 📊 Genetic testing confirms SH2D1A/SAP mutation.
⚕️ Management
- 💉 HSCT (haematopoietic stem cell transplantation) = only curative therapy; ideally performed early.
- 🚨 Aggressive management of acute EBV infections is lifesaving.
- 🧪 Immunoglobulin replacement therapy helps reduce infections in those with hypogammaglobulinemia.
- ⚖️ Supportive care: antivirals, chemotherapy for EBV-associated lymphomas, HLH-directed therapy if needed.
💡 Exam tip:
Think XLP in a young boy with fatal EBV mononucleosis, hypogammaglobulinemia, or early-onset lymphoma.
Distinguish from other immunodeficiencies: XLP is unique for its EBV-triggered catastrophic responses.
