Lymphoproliferative Syndrome, X-Linked, 2 (XLP2)

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OMIM 57 300635 Disease Ontology 12 DOID:0060706 ICD10 33 D82.3 MedGen 42 C1845076

MeSH 44 D008232 SNOMED-CT via HPO 69 11381005 263934009 16294009 304132006 306058006 386661006 50177009 64226004 234532001 119250001 234457009 111589005 128241005 119248009 61070002 32861005 more UMLS 73 C1845076

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)

MalaCards based summary : Lymphoproliferative Syndrome, X-Linked, 2, also known as xiap deficiency, is related to lymphoproliferative syndrome, x-linked, 1 and lymphoproliferative syndrome. An important gene associated with Lymphoproliferative Syndrome, X-Linked, 2 is XIAP (X-Linked Inhibitor Of Apoptosis), and among its related pathways/superpathways are Toll-like Receptor Signaling Pathway and Deubiquitination. The drugs Krestin and Pharmaceutical Solutions have been mentioned in the context of this disorder. Affiliated tissues include t cells, nk cells and skin, and related phenotypes are splenomegaly and fever

Disease Ontology : ¹² 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 : ⁷⁵ Lymphoproliferative syndrome, X-linked, 2: 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:

300635

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Synthetic lethal with MLN4924 (a NAE inhibitor)	GR00250-A-1	9.53	NOD1 NOD2 RIPK2 XIAP
2	Synthetic lethal with MLN4924 (a NAE inhibitor)	GR00250-A-2	9.53	NOD1 NOD2 RIPK2 XIAP

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