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.
Some patients with less common cellular immunodeficiencies may have severe immunodeficiency with early onset and significant morbidity and mortality, while others have only mild problems. Patients with these types of deficiencies have some defect in their T-cell (cellular) immune system, resulting in a different spectrum of infection problems than those individuals with typical antibody deficiency. These include deep-seated bacterial infections, viral and fungal infections, tuberculosis, and other mycobacterial infections. Cellular immunodeficiencies are usually more difficult to treat and may need cellular reconstitution via hematopoietic stem cell transplantation or, perhaps, gene therapy.
This page contains general medical and/or legal information that cannot be applied safely to any individual case. Medical and/or legal knowledge and practice can change rapidly. Therefore, this page should not be used as a substitute for professional medical and/or legal advice.
Adapted from the IDF Patient & Family Handbook for Primary Immunodeficiency Diseases, Sixth Edition.
Copyright ©2019 by Immune Deficiency Foundation, USA
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