X-linked lymphoproliferative syndrome

Synonyms: XLP, Duncan's disease, familial fatal Epstein-Barr virus infection, Purtilo's syndrome

This X-linked inherited disorder (thus affecting boys) resulting from a defective gene at Xq25 is characterised by a severe susceptibility to Epstein-Barr virus (EBV) infections.¹

Following exposure, 75% of patients develop a severe or fatal infectious mononucleosis. Survivors may go on to develop an acquired hypogammaglobulinaema, red cell aplasia, aplastic anaemia or lymphomatoid granulomatosis.²³

Presentation

Patients present in childhood (mean age 3-5 years) with signs of EBV infection:

• Respiratory: pharyngitis, lymphoid granulomatosis of lung.

• Abdomen: hepatomegaly, fulminant hepatitis and liver failure, splenomegaly.

• Haematological: atypical mononucleosis (lymphocytosis); thrombocytopenia or bone marrow failure.

• CNS: meningitis or encephalitis, hepatic encephalopathy.

Management

Bone marrow transplant is the definitive treatment.⁴⁵ Transplantation of cord-blood stem cells from an HLA-identical sibling has also been successful.⁶

There is research into the use of anti-CD20 rituximab (monoclonal antibody) in the acute phase of EBV infection which shows promise, and cytotoxic chemotherapy may also have a role.²

Genetic testing can identify affected individuals and carriers, and antenatal diagnosis is possible.

Complications

EBV infection can result in hepatic necrosis or bone marrow failure.

Later complications include hypogammaglobulinaemia, malignant lymphoma, aplastic anaemia or haemophagocytic syndrome.

Prognosis

Without transplant, 70% of patients will not survive beyond 10 years of age.¹