X-linked lymphoproliferative (XLP) syndromes 1 and 2

Gene: SH2D1A (XLP1) and XIAP (XLP2)

Inheritance pattern: X-linked recessive

XLP is characterized by lifelong vulnerability to Epstein-Barr virus (EBV) infection, which can lead to severe and fatal infectious mononucleosis, lymph node cancers (lymphomas), combined immunodeficiency and, less commonly, aplastic anemia (inability to produce red blood cells) or vasculitis (inflammation in the blood vessels). 

XLP is associated with a defect on the X chromosome termed SH2DIA and/or XIAP. As it is X-linked, this defect only affects males. (See chapter titled “Inheritance.”) Most patients with XLP do well until they are exposed to EBV. Then, they become seriously ill with fever, swollen lymph nodes, enlarged liver and spleen, and hepatitis. This infection triggers a condition called “hemophagocytic syndrome,” which also occurs in other immune deficiencies and can be fatal. If patients recover, they go on to develop one of the above-named problems.

Some patients are initially misdiagnosed with common variable immune deficiency (CVID). Early recognition is crucial since the disease can be cured by bone marrow or cord blood transplantation. Early screening of infant boys in families that have had children with XLP is also critically important so that they can be transplanted before contracting an EBV infection. There are two forms of this disorder: XLP1 due to defects in the SH2DIA gene, and XLP2 due to defects in the XIAP gene.