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.^2,3

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.^4,5 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

Document references

1. X-linked Lymphoproliferative Disorder, Online Mendelian Inheritance in Man (OMIM)
2. Seiter K et al; Lymphoproliferative Syndrome, X-linked, Medscape, Mar 2011
3. Purtilo DT, Sakamoto K, Barnabei V, et al; Epstein-Barr virus-induced diseases in boys with the X-linked lymphoproliferative syndrome (XLP): update on studies of the registry. Am J Med. 1982 Jul;73(1):49-56. [abstract]
4. Pracher E, Panzer-Grumayer ER, Zoubek A, et al; Successful bone marrow transplantation in a boy with X-linked lymphoproliferative syndrome and acute severe infectious mononucleosis. Bone Marrow Transplant. 1994 May;13(5):655-8. [abstract]
5. Hoffmann T, Heilmann C, Madsen HO, et al; Matched unrelated allogeneic bone marrow transplantation for recurrent malignant lymphoma in a patient with X-linked lymphoproliferative disease (XLP). Bone Marrow Transplant. 1998 Sep;22(6):603-4. [abstract]
6. Vowels MR, Tang RL, Berdoukas V, et al; Brief report: correction of X-linked lymphoproliferative disease by transplantation of cord-blood stem cells. N Engl J Med. 1993 Nov 25;329(22):1623-5.

Internet and further reading

• Arkwright PD, Makin G, Will AM, et al; X linked lymphoproliferative disease in a United Kingdom family. Arch Dis Child. 1998 Jul;79(1):52-5. [abstract]

Acknowledgements