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X-linked lymphoproliferative disease due to SH2D1A deficiency

Synonyms
Duncan disease; Duncan's syndrome; EBV infection severe susceptibility to; Epstein Barr virus infection familial fatal; IMMUNODEFICIENCY 5; IMMUNODEFICIENCY, X-LINKED PROGRESSIVE COMBINED VARIABLE; INFECTIOUS MONONUCLEOSIS, SEVERE, SUSCEPTIBILITY TO; Lymphoproliferative syndrome 1, X-linked; Purtilo syndrome; SH2D1A-Related Lymphoproliferative Disease, X-Linked
Modes of inheritance
X-linked recessive inheritance (Orphanet)

Summary

Excerpted from the GeneReview: X-Linked Lymphoproliferative Disease
X-linked lymphoproliferative disease (XLP) in general is 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). The condition primarily affects males. XLP has two recognizable subtypes, XLP1 (due to pathogenic variants in SH2D1A) and XLP2 (due to pathogenic variants in XIAP). HLH / fulminant infectious mononucleosis is the most common presentation regardless of subtype. HLH is characterized as an acute illness with prolonged and high fever, bi- or trilineage cytopenias, and hepatosplenomegaly, which is often severe or fatal. Death is generally secondary to liver failure or multisystem organ dysfunction. In those with XLP1, dys- or hypogammaglobulinemia can lead to varying degrees of humoral immune dysfunction associated with bronchiectasis and recurrent respiratory infections that, if untreated, may result in death. Lymphoproliferative disease (malignant lymphoma) and other lymphoproliferative diseases are specific to XLP1 and often develop in childhood, usually following EBV exposure. Rarer findings in those with XLP1 can include aplastic anemia, vasculitis, and lymphoid granulomatosis. Males with XLP2 are more likely to have HLH without EBV infection, recurrent episodes of HLH (which is not typically seen in those with XLP1), splenomegaly, and gastrointestinal disease, including enterocolitis and perirectal abscesses or fistulae. Rarely, individuals with XLP2 and inflammatory bowel disease have been reported to develop inflammatory liver disease, which can progress to fatal liver failure. Transient hypogammaglobulinemia has been rarely observed in those with XLP2. To date, neither lymphoproliferative disease nor common variable immunodeficiency has been reported in males with XLP2. Heterozygous females rarely have symptoms. There are, however, increasing numbers of reports of affected females with unfavorable (skewed) X-chromosome inactivation favoring the X chromosome with the pathogenic variant who develop HLH, inflammatory bowel disease, and erythema nodosum.
Full text of GeneReview (by section):
Summary
Diagnosis
Clinical Characteristics
Genetically Related (Allelic) Disorders
Differential Diagnosis
Management
Genetic Counseling
Resources
Molecular Genetics
Chapter Notes
References
Authors:
Lauren Meyer
Melissa Hines
Kejian Zhang
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Available tests

66 tests are in the database for this condition.

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Clinical tests (66 available)

Molecular Genetics Tests

Genes See tests for all associated and related genes

  • Also known as: DSHP, EBVS, IMD5, LYP, MTCP1, SAP, SAP/SH2D1A, XLP, XLPD, XLPD1, SH2D1A
    Summary: SH2 domain containing 1A

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

Clinical features

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Imported from Human Phenotype Ontology (HPO)

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