X-linked lymphoproliferative syndrome (XLP)

(also known as , Duncan’s syndrome)

An immunodeficiency due (in 50% of cases) to SLAM associated protein (SAP) defect, specifically affecting the handling of EBV, affected boys are normal until they meet the virus. Following infection, they develop profound secondary immune deficiency affecting T and NK cell function and antibody responses. The following clinical patterns (not mutually exclusive) are described (and can be presenting features):

  • severe infectious mononucleosis
  • malignant B cell lymphoma (ie monoclonal proliferation)
  • Lymphoproliferation viz hepatosplenomegaly (ie polyclonal proliferation)
  • aplastic anemia
  • panhypogammaglobulinemia
  • haemophagocytic lymphohistiocytosis (HLH)
  • vasculitis

The prognosis is very poor with 75-85% mortality. Confirmation of the diagnosis involves demonstrating EB virus genome in lymphocytes by DNA hybridization, without antibody response to EB nuclear antigen (EBNA). The mothers of affected boys also have abnormal EB virus serology, with persisting very high titers against viral capsid antigen. Treatment is with Rituximab (anti CD20), although EBV receptor is CD21. If diagnosed in a sibling before they are infected by the virus, regular IVIG as passive immunization can be attempted though its efficacy is unproven.

Autosomal forms have been described.

OMIM entry