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X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia(XMEN)

MedGen UID:
477076
Concept ID:
C3275445
Disease or Syndrome
Synonyms: IMMUNODEFICIENCY, X-LINKED, WITH MAGNESIUM DEFECT, EPSTEIN-BARR VIRUS INFECTION, AND NEOPLASIA; XMEN
SNOMED CT: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia (711481001)
Modes of inheritance:
Unknown inheritance
MedGen UID:
989040
Concept ID:
CN307042
Finding
Source: Orphanet
Hereditary clinical entity whose mode of inheritance is unknown.
 
Gene (location): MAGT1 (Xq21.1)
 
Monarch Initiative: MONDO:0010455
OMIM®: 300853
Orphanet: ORPHA317476

Definition

XMEN is an X-linked recessive immunodeficiency characterized by CD4 (186940) lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation (Li et al., 2011). Affected individuals have chronic Epstein-Barr virus (EBV) infection and are susceptible to the development of EBV-associated B-cell lymphoproliferative disorders. Magnesium supplementation may be therapeutic (summary by Li et al., 2014). [from OMIM]

Additional description

From MedlinePlus Genetics
X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym XMEN) is a disorder that affects the immune system in males. In XMEN, certain types of immune system cells called T cells are reduced in number or do not function properly. Normally these cells recognize foreign invaders, such as viruses, bacteria, and fungi, and are then turned on (activated) to attack these invaders in order to prevent infection and illness. Because males with XMEN do not have enough functional T cells, they have frequent infections, such as ear infections, sinus infections, and pneumonia.

In particular, affected individuals are vulnerable to the Epstein-Barr virus (EBV). EBV is a very common virus that infects more than 90 percent of the general population and in most cases goes unnoticed. Normally, after initial infection, EBV remains in the body for the rest of a person's life. However, the virus is generally inactive (latent) because it is controlled by T cells. In males with XMEN, however, the T cells cannot control the virus, and EBV infection can lead to cancers of immune system cells (lymphomas). The word "neoplasia" in the condition name refers to these lymphomas; neoplasia is a general term meaning abnormal growths of tissue. The EBV infection itself usually does not cause any other symptoms in males with XMEN, and affected individuals may not come to medical attention until they develop lymphoma.  https://medlineplus.gov/genetics/condition/x-linked-immunodeficiency-with-magnesium-defect-epstein-barr-virus-infection-and-neoplasia

Clinical features

From HPO
Classic Hodgkin lymphoma
MedGen UID:
9283
Concept ID:
C0019829
Neoplastic Process
Classic Hodgkin lymphoma is a lymph node cancer of germinal center B-cell origin. Hodgkin lymphoma tumors consist of a minority of malignant cells, known as 'Reed-Sternberg' (RS) cells, mixed with reactive lymphocytes and other benign inflammatory cells. A defining feature of RS cells is the presence of 2 nuclei (summary by Salipante et al., 2009).
Lymphoma
MedGen UID:
44223
Concept ID:
C0024299
Neoplastic Process
A cancer originating in lymphocytes and presenting as a solid tumor of lymhpoid cells.
Lymphoproliferative disorder
MedGen UID:
6162
Concept ID:
C0024314
Neoplastic Process
A disorder characterized by proliferation of lymphocytes at various stages of differentiation. Lymphoproliferative disorders can be neoplastic (clonal, as in lymphomas and leukemias) or reactive (polyclonal, as in infectious mononucleosis).
B-cell lymphoma
MedGen UID:
86953
Concept ID:
C0079731
Neoplastic Process
A type of lymphoma that originates in B-cells.
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Recurrent sinusitis
MedGen UID:
107919
Concept ID:
C0581354
Disease or Syndrome
A recurrent form of sinusitis.
Recurrent bronchitis
MedGen UID:
148159
Concept ID:
C0741796
Disease or Syndrome
An increased susceptibility to bronchitis as manifested by a history of recurrent bronchitis.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Autoimmune thrombocytopenia
MedGen UID:
116621
Concept ID:
C0242584
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Decreased CD4:CD8 ratio
MedGen UID:
163125
Concept ID:
C0853905
Finding
An abnormal reduction of the relative proportion of CD4+ to CD8+ T cells.
Recurrent viral infections
MedGen UID:
332357
Concept ID:
C1837066
Finding
Increased susceptibility to viral infections, as manifested by recurrent episodes of viral infection.
Decreased T cell activation
MedGen UID:
339550
Concept ID:
C1846550
Finding
Decreased or impaired activation of T cells in response to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
Persistent EBV viremia
MedGen UID:
767466
Concept ID:
C3554552
Finding
Persistent presence of Epstein-Barr virus in the blood.
Decreased specific anti-polysaccharide antibody level
MedGen UID:
867382
Concept ID:
C4021747
Finding
The presence of normal overall immunoglobulin levels with deficiency of specific immunoglobulins directed against bacterial polysaccharides.
Decreased CD69 upregulation upon TCR activation
MedGen UID:
1625084
Concept ID:
C4531236
Cell or Molecular Dysfunction
Reduced or impaired upregulation of CD69 on T cells after activation via the T cell receptor (TCR).
Severe varicella zoster infection
MedGen UID:
1688785
Concept ID:
C5139168
Disease or Syndrome
An unusually severe form of varicella zoster virus (VZV) infection. In the majority of the cases, especially in children, varicella is a very mild infection characterized by skin lesions, low grade fever and malaise. Severe infection is characterized by manifestations including VZV pneumonia, hepatitis, meningitis, and disseminated varicella.
Chronic active Epstein-Barr virus infection
MedGen UID:
1695472
Concept ID:
C5139190
Disease or Syndrome
Chronic active Epstein-Barr virus (EBV) infection is an uncommon outcome of EBV infection and may present as a waxing and waning or fulminant syndrome. Unlike acute infectious mononucleosis, wherein EBV establishes lifelong infection and survives by maintaining a delicate balance with the host as a latent infection, in chronic active EBV infection the host-virus balance is disturbed.
Decreased proportion of CD4-positive T cells
MedGen UID:
1698933
Concept ID:
C5139203
Finding
A reduction in the proportion of CD4-positive T cells relative to the total number of T cells.
Persistent CMV viremia
MedGen UID:
1696514
Concept ID:
C5139221
Finding
Lasting (uncontrolled) presence of cytomegalovirus in the blood circulation.
Decreased proportion of CD4-positive helper T cells
MedGen UID:
1719772
Concept ID:
C5235140
Finding
A decreased proportion of circulating CD4-positive helper T cells relative to total T cell count.
Mediastinal lymphadenopathy
MedGen UID:
451062
Concept ID:
C0520743
Disease or Syndrome
Swelling of lymph nodes within the mediastinum, the central compartment of the thoracic cavities that contains the heart and the great vessels, the esophagus, and trachea and other structures including lymph nodes.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVX-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia
Follow this link to review classifications for X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia in Orphanet.

Professional guidelines

PubMed

Li FY, Chaigne-Delalande B, Rao VK, Zhang Y, Matthews H, Kuijpers TT, Su H, Uzel G, Lenardo MJ
Eur J Hum Genet 2015 Jun;23(6):889-. Epub 2014 Sep 10 doi: 10.1038/ejhg.2014.179. PMID: 25205404Free PMC Article

Recent clinical studies

Etiology

Chauvin SD, Price S, Zou J, Hunsberger S, Brofferio A, Matthews H, Similuk M, Rosenzweig SD, Su HC, Cohen JI, Lenardo MJ, Ravell JC
J Clin Immunol 2022 Jan;42(1):108-118. Epub 2021 Oct 16 doi: 10.1007/s10875-021-01137-w. PMID: 34655400Free PMC Article
Angenendt L, Hilgefort I, Mikesch JH, Schlüter B, Berdel WE, Lenz G, Stelljes M, Schliemann C
Ann Hematol 2021 Jul;100(7):1871-1878. Epub 2020 Dec 19 doi: 10.1007/s00277-020-04382-y. PMID: 33341918Free PMC Article
Brault J, Meis RJ, Li L, Bello E, Liu T, Sweeney CL, Koontz SM, Dowdell K, Theobald N, Lee J, Allen C, Clark AB, Ravell JC, Lenardo MJ, Dahl GA, Malech HL, De Ravin SS
Cytotherapy 2021 Mar;23(3):203-210. Epub 2020 Oct 10 doi: 10.1016/j.jcyt.2020.08.013. PMID: 33051095
Gile J, Ruan G, Abeykoon J, McMahon MM, Witzig T
Blood Rev 2020 Nov;44:100676. Epub 2020 Mar 27 doi: 10.1016/j.blre.2020.100676. PMID: 32229066
Ravell J, Chaigne-Delalande B, Lenardo M
Curr Opin Pediatr 2014 Dec;26(6):713-9. doi: 10.1097/MOP.0000000000000156. PMID: 25313976Free PMC Article

Diagnosis

Benavides D, Ebrahim A, Ravell JC, Lenardo M, Gahl WA, Toro C
J Neuroimmunol 2024 Jan 15;386:578251. Epub 2023 Nov 24 doi: 10.1016/j.jneuroim.2023.578251. PMID: 38041964Free PMC Article
Trapani V, Shomer N, Rajcan-Separovic E
Magnes Res 2015 Jun;28(2):46-55. PMID: 26422833
Li FY, Chaigne-Delalande B, Rao VK, Zhang Y, Matthews H, Kuijpers TT, Su H, Uzel G, Lenardo MJ
Eur J Hum Genet 2015 Jun;23(6):889-. Epub 2014 Sep 10 doi: 10.1038/ejhg.2014.179. PMID: 25205404Free PMC Article
Ravell J, Chaigne-Delalande B, Lenardo M
Curr Opin Pediatr 2014 Dec;26(6):713-9. doi: 10.1097/MOP.0000000000000156. PMID: 25313976Free PMC Article
Li FY, Chaigne-Delalande B, Su H, Uzel G, Matthews H, Lenardo MJ
Blood 2014 Apr 3;123(14):2148-52. Epub 2014 Feb 18 doi: 10.1182/blood-2013-11-538686. PMID: 24550228Free PMC Article

Therapy

Chauvin SD, Price S, Zou J, Hunsberger S, Brofferio A, Matthews H, Similuk M, Rosenzweig SD, Su HC, Cohen JI, Lenardo MJ, Ravell JC
J Clin Immunol 2022 Jan;42(1):108-118. Epub 2021 Oct 16 doi: 10.1007/s10875-021-01137-w. PMID: 34655400Free PMC Article
Angenendt L, Hilgefort I, Mikesch JH, Schlüter B, Berdel WE, Lenz G, Stelljes M, Schliemann C
Ann Hematol 2021 Jul;100(7):1871-1878. Epub 2020 Dec 19 doi: 10.1007/s00277-020-04382-y. PMID: 33341918Free PMC Article

Prognosis

Bąbol-Pokora K, Wołowiec M, Popko K, Jaworowska A, Bryceson YT, Tesi B, Henter JI, Młynarski W, Badowska W, Balwierz W, Drabko K, Kałwak K, Maciejka-Kembłowska L, Pieczonka A, Sobol-Milejska G, Kołtan S, Malinowska I; Polish Pediatric Hematology, Oncology Society
Arch Immunol Ther Exp (Warsz) 2021 Oct 22;69(1):31. doi: 10.1007/s00005-021-00635-4. PMID: 34677667Free PMC Article
Angenendt L, Hilgefort I, Mikesch JH, Schlüter B, Berdel WE, Lenz G, Stelljes M, Schliemann C
Ann Hematol 2021 Jul;100(7):1871-1878. Epub 2020 Dec 19 doi: 10.1007/s00277-020-04382-y. PMID: 33341918Free PMC Article
Gile J, Ruan G, Abeykoon J, McMahon MM, Witzig T
Blood Rev 2020 Nov;44:100676. Epub 2020 Mar 27 doi: 10.1016/j.blre.2020.100676. PMID: 32229066
Dhalla F, Murray S, Sadler R, Chaigne-Delalande B, Sadaoka T, Soilleux E, Uzel G, Miller J, Collins GP, Hatton CS, Bhole M, Ferry B, Chapel HM, Cohen JI, Patel SY
J Clin Immunol 2015 Feb;35(2):112-8. Epub 2014 Dec 13 doi: 10.1007/s10875-014-0116-2. PMID: 25504528Free PMC Article

Clinical prediction guides

Golloshi K, Mitchell W, Kumar D, Malik S, Parikh S, Aljudi AA, Castellino SM, Chandrakasan S
J Clin Immunol 2024 Jun 19;44(7):153. doi: 10.1007/s10875-024-01749-y. PMID: 38896122
Chauvin SD, Price S, Zou J, Hunsberger S, Brofferio A, Matthews H, Similuk M, Rosenzweig SD, Su HC, Cohen JI, Lenardo MJ, Ravell JC
J Clin Immunol 2022 Jan;42(1):108-118. Epub 2021 Oct 16 doi: 10.1007/s10875-021-01137-w. PMID: 34655400Free PMC Article
Matsuda-Lennikov M, Biancalana M, Zou J, Ravell JC, Zheng L, Kanellopoulou C, Jiang P, Notarangelo G, Jing H, Masutani E, Oler AJ, Olano LR, Schulz BL, Lenardo MJ
J Biol Chem 2019 Sep 13;294(37):13638-13656. Epub 2019 Jul 23 doi: 10.1074/jbc.RA119.008903. PMID: 31337704Free PMC Article

Recent systematic reviews

Golloshi K, Mitchell W, Kumar D, Malik S, Parikh S, Aljudi AA, Castellino SM, Chandrakasan S
J Clin Immunol 2024 Jun 19;44(7):153. doi: 10.1007/s10875-024-01749-y. PMID: 38896122

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