X-linked lymphoproliferative syndrome results from a T-cell and natural killer cell defect and is characterized by an abnormal response to Epstein-Barr virus infection, leading to liver failure, immunodeficiency, lymphoma, fatal lymphoproliferative disease, or bone marrow aplasia.

X-linked lymphoproliferative syndrome is caused by mutations in a gene on the X chromosome that encodes a T and natural killer (NK) cell–specific protein called SAP. Without SAP, lymphocytes proliferate unchecked in response to Epstein-Barr virus (EBV) infection, and NK cells do not function.

The syndrome is usually asymptomatic until EBV infection develops. Then, most patients develop fulminating or fatal infectious mononucleosis with liver failure (caused by cytotoxic T cells that react to EBV-infected B or other tissue cells); survivors of initial infection develop B-cell lymphomas, aplastic anemia, hypogammaglobulinemia (resembling that in common variable immunodeficiency), or a combination.

Diagnosis

Diagnostic findings in patients that survive initial EBV infection include hypogammaglobulinemia, decreased antibody responses to antigens (particularly to EBV nuclear antigen), impaired T-cell proliferative responses to mitogens, decreased NK-cell function, and an inverted CD4:CD8 ratio. Genetic diagnosis by mutation analysis is possible before EBV infection and symptoms develop.

Treatment

About 75% of patients die by age 10, and all die by age 40 unless bone marrow transplantation is done. Transplantation is curative if done before EBV infection or other disorders become irreversible, resulting in death.

Last full review/revision September 2008 by Rebecca H. Buckley, MD