Lymphoproliferative Syndrome, X-Linked, 2 (XLP2)

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OMIM®: ⁵⁷ XLP2 is an X-linked primary immune deficiency with symptom onset usually in the first years of life, although later onset may occur. Features are compatible with immune dysregulation and include hemophagocytic lymphohistiocytosis (HLH), often associated with chronic Epstein-Barr virus (EBV) infection, splenomegaly, fever, colitis or inflammatory bowel disease (IBD), and recurrent infections. Laboratory abnormalities are variable, but can include hypogammaglobulinemia, cytopenias, and low levels of a particular subset of T cells known as NKT (or iNKT) cells. Functional studies show increased sensitivity of T cells to apoptosis (activation-induced cell death, AICD), impaired cytokine production, including of TNF-alpha (TNFA; 191160), and general dysregulation of the immune pathway, such as increased levels of IL18 (600953). However, circulating levels of lymphocytes and NK cells are usually normal. Many patients die from fulminant HLH, and the only curative treatment is a hematopoietic stem cell transplant, although this procedure has been associated with a poor prognosis. Female mutation carriers are usually asymptomatic, although some female carriers may have less severe manifestations, which appears to depend on X-inactivation patterns (summary by Yang et al., 2012; review by Latour and Aguilar, 2015). Latour and Aguilar (2015) provided a detailed review of XIAP deficiency, including clinical features, molecular genetics, and pathophysiology. For a general phenotypic description and a discussion of genetic heterogeneity of X-linked lymphoproliferative syndrome, see XLP1 (308240). (300635) (Updated 08-Dec-2022)

MalaCards based summary: Lymphoproliferative Syndrome, X-Linked, 2, also known as xlp2, is related to hemophagocytic lymphohistiocytosis, familial, 1 and enterocolitis. An important gene associated with Lymphoproliferative Syndrome, X-Linked, 2 is XIAP (X-Linked Inhibitor Of Apoptosis), and among its related pathways/superpathways are Innate Immune System and NF-kappaB Signaling. The drugs polysaccharide-K and Pharmaceutical Solutions have been mentioned in the context of this disorder. Affiliated tissues include t cells, b cells and nk cells, and related phenotypes are splenomegaly and fever

GARD: ¹⁹ X-linked lymphoproliferative disease (XLP) has two recognizable subtypes, XLP1 and XLP2. XLP1 is characterized predominantly by one of three commonly recognized phenotypes: Inappropriate immune response to Epstein-Barr virus (EBV) infection leading to hemophagocytic lymphohistiocytosis (HLH) or severe mononucleosis. Dysgammaglobulinemia. Lymphoproliferative disease (malignant lymphoma). XLP2 is most often characterized by HLH (often associated with EBV), dysgammaglobulinemia, and inflammatory bowel disease. HLH resulting from EBV infection is associated with an unregulated and exaggerated immune response with widespread proliferation of cytotoxic T cells, EBV-infected B cells, and macrophages. Dysgammaglobulinemia is typically hypogammaglobulinemia of one or more immunoglobulin subclasses. The malignant lymphomas are typically B-cell lymphomas, non-Hodgkin type, often extranodal, and in particular involving the intestine.

Orphanet: ⁵⁸ A rare, genetic, primary immunodeficiency disorder characterized by an abnormal immune response to Epstein-Barr virus (EBV) infection, caused by hemizygous mutations in the X-linked XIAP gene, resulting in B cell lymphoproliferation and manifestating with various phenotypes which include EBV-driven hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, recurrent splenomegaly, hepatitis, colitis, and intestinal bowel disease with features of Crohn's disease. Additional manifestations include variable auto-inflammatory symptoms such as uveitis, arthritis, skin abscesses, erythema nodosum, and nephritis. Neurological involvement is rare and lymphoma is never observed. Laboratory findings include normal or increased activated T cells, low or normal iNKT cells, and normal or reduced memory B cells.

Disease Ontology: ¹¹ A lymphoproliferative syndrome characterized by X-linked inheritance, immune dysregulation after viral infect that may include lymphohystiocytosis, hypogammaglobulinemia and/or splenomegaly and that has material basis in mutation in the XIAP gene on chromosome Xq25.

UniProtKB/Swiss-Prot: ⁷³ A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.

Clinical features from OMIM®:

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