GTR Home > Conditions/Phenotypes > X-linked lymphoproliferative syndrome 1

Disease characteristics

Excerpted from the GeneReview: Lymphoproliferative Disease, X-Linked
X-linked lymphoproliferative disease (XLP) is caused by mutations in SH2D1A and XIAP (BIRC4). XLP may also occur in rare instances with no identified underlying genetic cause. The three most commonly recognized phenotypes of SH2D1A-related XLP are hemophagocytic lymphohistiocytosis (HLH) associated with Epstein-Barr virus (EBV) infection (58% of individuals), dysgammaglobulinemia (31%), and lymphoproliferative disorders (malignant lymphoma) (30%). Manifestations of SH2D1A-related XLP, including HLH, can also occur in the absence of EBV. XIAP-related XLP also presents with HLH (often associated with EBV) or dysgammaglobulinemia, but no cases of lymphoma have been described to date. HLH resulting from EBV infection, sometimes referred to as severe infectious mononucleosis, is associated with an unregulated and exaggerated immune response with widespread proliferation of cytotoxic T cells, EBV-infected B cells, and macrophages. Fulminant hepatitis, hepatic necrosis, and profound bone marrow failure are typical, resulting in mortality that is higher than 90%, though prompt recognition of the disorder and aggressive treatment interventions likely improve survival. Dysgammaglobulinemia is typically hypogammaglobulinemia of one or more immunoglobulin subclasses. The prognosis is improved if affected males are managed with regular intravenous immunoglobulin (IVIG) therapy. The malignant lymphomas are typically high-grade B cell lymphomas, non-Hodgkin type, often extranodal, and in particular involving the intestine.

Available tests

21 tests are in the database for this condition. Compare labs offering these tests.

Check Associated genes for additional relevant tests.

Associated genes

  • Also known as: RP5-1052M9.3, DSHP, EBVS, IMD5, LYP, MTCP1, SAP, SAP/SH2D1A, XLP, XLPD, XLPD1, SH2D1A
    Summary: SH2 domain containing 1A

  • Also known as: RP1-315G1.5, API3, BIRC4, IAP-3, ILP1, MIHA, XLP2, hIAP-3, hIAP3, XIAP
    Summary: X-linked inhibitor of apoptosis

Clinical features

Help
  • Splenomegaly
  • Thrombocytopenia
  • Anemia
  • Lymphadenopathy
  • Reduced natural killer cell activity
  • IgG deficiency
  • Meningitis
  • Pancytopenia
  • Hepatomegaly
  • Encephalitis
  • Hepatic encephalopathy
  • Lymphoma
  • Immunodeficiency
  • Increased IgM level
  • Fulminant hepatitis
  • Recurrent pharyngitis
Show all (16)

IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Write to the Help Desk