X-Linked Lymphoproliferative Syndrome

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Retrieved

2022-04-26

Source

Gard

Trials

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Genes

SH2D1A, IL17A, XIAP, IFNG, STAG2, SLAMF1, APCS, IL10, HPRT1, ITK, RTEL1, CD244, CD1D, ICOS, CCR4, TRBV20OR9-2, NR0B2, CD84, TENM1, HPGDS, IL22, RAB27A, FOXP3, AP5M1, NLRC4, IL21, SLAMF6, VPS13B, CD2, PTPN6, PTPN11, IL2RG, DOK1, FUT1, HLA-DQB1, LYST, IL1A, IL1B, IL1RN, IL4, CYBB, IL7R, CD40LG, INS, CD27, PDCD1, SERPINA4, PLCG1, NCF1

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X-linked lymphoproliferative syndrome (XLP) is an immune system disorder that occurs almost exclusively in males. People with XLP have an increased risk of infection because their body cannot properly regulate the number of immune system cells (lymphocytes) and blood cells. The symptoms associated with XLP vary from person to person, and even among family members. In most cases, symptoms begin anywhere from 6 months of age to 10 years of age. XLP generally has two subtypes, which are caused by mutations in different genes:

XLP1 is mainly characterized by an inappropriate immune response to Epstein-Barr virus (EBV) infection, leading to hemophagocytic lymphohistiocytosis (HLH) or severe mononucleosis; dysgammaglobulinemia; and lymphoproliferative disease (malignant lymphoma).
XLP2 is usually characterized by HLH (often associated with EBV), dysgammaglobulinemia, and inflammatory bowel disease (colitis). People with XLP2 have not been known to develop lymphoma.

Signs and symptoms of HLH include fever, enlarged lymph nodes and spleen, skin rashes, and problems with the lungs, digestive system, liver, and nervous system. The heart, kidneys, or other organs may also be affected. Mononucleosis may cause fatigue; fever; an inflamed and sore throat; enlarged lymph nodes, liver, and spleen; and symptoms of anemia. Dysgammaglobulinemia causes an increased risk of recurrent infections.

XLP1 is caused by mutations in the SH2D1A gene, and XLP2 is caused by mutations in the XIAP gene. Inheritance is X-linked recessive. However, in rare cases, females with a mutation on one copy of the responsible gene develop symptoms of XLP. A diagnosis of either type of XLP can be confirmed with genetic testing. Of note, there have been males with mutations known to cause XLP that have not developed symptoms.

The only cure for XLP is allogeneic hematopoietic cell transplantation, which should be considered as early as possible. Treatment of XLP-related HLH may include immunosuppressive agents (such as steroids and etoposide or anti-thymocyte globulin), and rituximab when HLH is associated with EBV infection. Hypogammaglobulinemia is treated with IVIG replacement therapy, and lymphoma is treated with standard chemotherapy. Inflammatory bowel disease is treated with immunosuppression.

Without treatment, many people with XLP do not survive beyond childhood, usually due to HLH. The average age of death for males has been reported as 11 years (with a range of 2-69 years) for XLP1, and 16 years (with a range of 1-52 years) for XLP2.