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Monocytopenia with susceptibility to infections(DCML; MONOMAC; IMD21)

MedGen UID:
481660
Concept ID:
C3280030
Disease or Syndrome
Synonyms: COMBINED IMMUNODEFICIENCY WITH SUSCEPTIBILITY TO MYCOBACTERIAL, VIRAL, AND FUNGAL INFECTIONS; Dendritic cell, monocyte, B lymphocyte, and natural killer lymphocyte deficiency; GATA2 DEFICIENCY; IMMUNODEFICIENCY 21; MONOCYTOPENIA AND MYCOBACTERIAL INFECTION SYNDROME; MONOCYTOPENIA WITH SUSCEPTIBILITY TO MYCOBACTERIAL, FUNGAL, AND PAPILLOMAVIRUS INFECTIONS AND MYELODYSPLASIA
SNOMED CT: Monocyte-B natural killer dendritic cell deficiency syndrome (778024005); Combined immunodeficiency with susceptibility to mycobacterial, viral and fungal infection (778024005); Monocytopenia and mycobacterial infection syndrome (778024005); Dendritic cell, monocyte, B and NK lymphoid deficiency (778024005); MonoMAC (778024005); Monocytopenia with susceptibility to infections (778024005)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): GATA2 (3q21.3)
 
Monarch Initiative: MONDO:0013607
OMIM®: 614172
Orphanet: ORPHA228423

Definition

This primary immunodeficiency, designated IMD21, DCML, or MONOMAC, is characterized by profoundly decreased or absent monocytes, B lymphocytes, natural killer (NK) lymphocytes, and circulating and tissue dendritic cells (DCs), with little or no effect on T-cell numbers. Clinical features of IMD21 are variable and include susceptibility to disseminated nontuberculous mycobacterial infections, papillomavirus infections, opportunistic fungal infections, and pulmonary alveolar proteinosis. Bone marrow hypocellularity and dysplasia of myeloid, erythroid, and megakaryocytic lineages are present in most patients, as are karyotypic abnormalities, including monosomy 7 and trisomy 8. In the absence of cytogenetic abnormalities or overt dysplasia, hypoplastic bone marrow may initially be diagnosed as aplastic anemia. Bone marrow transplantation is the only cure. Some patients may have an increased risk of miscarriage. Both autosomal dominant transmission and sporadic cases occur. Less common manifestations of GATA2 deficiency include lymphedema and sensorineural hearing loss, a phenotype usually termed 'Emberger syndrome' (614038) (summary by Bigley et al. (2011), Hsu et al. (2011), and Spinner et al. (2014)). [from OMIM]

Clinical features

From HPO
Myeloid leukemia
MedGen UID:
7320
Concept ID:
C0023470
Neoplastic Process
A leukemia that originates from a myeloid cell, that is the blood forming cells of the bone marrow.
Myelodysplasia
MedGen UID:
10231
Concept ID:
C0026985
Congenital Abnormality
Clonal hematopoietic stem cell disorders characterized by dysplasia (ineffective production) in one or more hematopoietic cell lineages, leading to anemia and cytopenia.
Cervical intraepithelial neoplasia
MedGen UID:
60214
Concept ID:
C0206708
Neoplastic Process
A precancerous condition characterized by dysplasia of the cervical epithelium. Cervical intraepithelial neoplasia (CIN) 1, 2 and 3 based on its relationship with the prognosis. CIN 1 is mild dysplasia, which is mostly observed because it disappears as part of its natural course. CIN 3 includes severe dysplasia and carcinoma in situ, and management involves treatment because it is highly likely to develop into invasive cancer.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Aplastic anemia
MedGen UID:
8063
Concept ID:
C0002874
Disease or Syndrome
Aplastic anemia is a serious disorder of the bone marrow that affects between 2 and 5 persons per million per year. About 75% of these cases are classified as idiopathic (Young, 2000). In about 15% of cases a drug or infection can be identified that precipitates the aplasia, although why only some individuals are susceptible is unclear. In about 5 to 10% of patients, the aplastic anemia is constitutional--i.e., is familial or presents with one or more associated somatic abnormalities (summary by Vulliamy et al., 2002).
Megakaryocyte nucleus hypolobulation
MedGen UID:
1614231
Concept ID:
C4531162
Finding
The presence of megakaryocytes in the bone marrow whose nuclei are less lobulated than expected for the size of the nucleus.
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.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Osteomyelitis
MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism.
Monocytopenia
MedGen UID:
507013
Concept ID:
C0427544
Finding
An decreased number of circulating monocytes.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Recurrent mycobacterium avium complex infections
MedGen UID:
853464
Concept ID:
C1737260
Finding
Increased susceptibility to mycobacterial avium complex infections, as manifested by recurrent episodes of mycobacterial infection.
Recurrent viral infections
MedGen UID:
332357
Concept ID:
C1837066
Finding
Increased susceptibility to viral infections, as manifested by recurrent episodes of viral infection.
Recurrent fungal infections
MedGen UID:
336166
Concept ID:
C1844384
Disease or Syndrome
Increased susceptibility to fungal infections, as manifested by multiple episodes of fungal infection.
B lymphocytopenia
MedGen UID:
340780
Concept ID:
C1855067
Finding
An abnormal decrease from the normal count of B cells.
Reduced natural killer cell count
MedGen UID:
383765
Concept ID:
C1855767
Finding
Less than normal number of natural killer cells, a type of lymphocyte in the innate immune system with an ability to mediate cytotoxicity and produce cytokines after the ligation of a germline-encoded activation receptor.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMonocytopenia with susceptibility to infections
Follow this link to review classifications for Monocytopenia with susceptibility to infections in Orphanet.

Professional guidelines

PubMed

Roncareggi S, Girardi K, Fioredda F, Pedace L, Arcuri L, Badolato R, Bonanomi S, Borlenghi E, Cirillo E, Coliva T, Consonni F, Conti F, Farruggia P, Gambineri E, Guerra F, Locatelli F, Mancuso G, Marzollo A, Masetti R, Micalizzi C, Onofrillo D, Piccini M, Pignata C, Raddi MG, Santini V, Vendemini F, Biondi A, Saettini F
J Clin Immunol 2023 Nov;43(8):2192-2207. Epub 2023 Oct 14 doi: 10.1007/s10875-023-01583-8. PMID: 37837580
Freeman AF
J Pediatric Infect Dis Soc 2018 Dec 26;7(suppl_2):S79-S82. doi: 10.1093/jpids/piy114. PMID: 30590619Free PMC Article
Seidel MG
Blood 2014 Oct 9;124(15):2337-44. Epub 2014 Aug 27 doi: 10.1182/blood-2014-06-583260. PMID: 25163701Free PMC Article

Recent clinical studies

Etiology

Cheloor Kovilakam S, Gu M, Dunn WG, Marando L, Barcena C, Nik-Zainal S, Mohorianu I, Kar SP, Fabre MA, Quiros PM, Vassiliou GS
Blood 2023 Oct 5;142(14):1185-1192. doi: 10.1182/blood.2023020209. PMID: 37506341
Sahoo SS, Kozyra EJ, Wlodarski MW
Best Pract Res Clin Haematol 2020 Sep;33(3):101197. Epub 2020 Jul 29 doi: 10.1016/j.beha.2020.101197. PMID: 33038986Free PMC Article
Bluteau O, Sebert M, Leblanc T, Peffault de Latour R, Quentin S, Lainey E, Hernandez L, Dalle JH, Sicre de Fontbrune F, Lengline E, Itzykson R, Clappier E, Boissel N, Vasquez N, Da Costa M, Masliah-Planchon J, Cuccuini W, Raimbault A, De Jaegere L, Adès L, Fenaux P, Maury S, Schmitt C, Muller M, Domenech C, Blin N, Bruno B, Pellier I, Hunault M, Blanche S, Petit A, Leverger G, Michel G, Bertrand Y, Baruchel A, Socié G, Soulier J
Blood 2018 Feb 15;131(7):717-732. Epub 2017 Nov 16 doi: 10.1182/blood-2017-09-806489. PMID: 29146883
Cohen JI
Curr Top Microbiol Immunol 2015;390(Pt 1):241-65. doi: 10.1007/978-3-319-22822-8_10. PMID: 26424649Free PMC Article
Hsu AP, McReynolds LJ, Holland SM
Curr Opin Allergy Clin Immunol 2015 Feb;15(1):104-9. doi: 10.1097/ACI.0000000000000126. PMID: 25397911Free PMC Article

Diagnosis

Henrie R, Cherniawsky H, Marcon K, Zhao EJ, Marinkovic A, Pourshahnazari P, Parkin S, Chen LYC
Am J Physiol Cell Physiol 2022 Oct 1;323(4):C1121-C1136. Epub 2022 Aug 8 doi: 10.1152/ajpcell.00356.2021. PMID: 35938681
Sahoo SS, Kozyra EJ, Wlodarski MW
Best Pract Res Clin Haematol 2020 Sep;33(3):101197. Epub 2020 Jul 29 doi: 10.1016/j.beha.2020.101197. PMID: 33038986Free PMC Article
Mangaonkar AA, Patnaik MM
Mayo Clin Proc 2020 Jul;95(7):1482-1498. Epub 2020 Jun 19 doi: 10.1016/j.mayocp.2019.12.013. PMID: 32571604
Rafei H, DiNardo CD
Best Pract Res Clin Haematol 2019 Jun;32(2):163-176. Epub 2019 May 3 doi: 10.1016/j.beha.2019.05.001. PMID: 31203998Free PMC Article
Bluteau O, Sebert M, Leblanc T, Peffault de Latour R, Quentin S, Lainey E, Hernandez L, Dalle JH, Sicre de Fontbrune F, Lengline E, Itzykson R, Clappier E, Boissel N, Vasquez N, Da Costa M, Masliah-Planchon J, Cuccuini W, Raimbault A, De Jaegere L, Adès L, Fenaux P, Maury S, Schmitt C, Muller M, Domenech C, Blin N, Bruno B, Pellier I, Hunault M, Blanche S, Petit A, Leverger G, Michel G, Bertrand Y, Baruchel A, Socié G, Soulier J
Blood 2018 Feb 15;131(7):717-732. Epub 2017 Nov 16 doi: 10.1182/blood-2017-09-806489. PMID: 29146883

Therapy

Desai SR, Chakraborty S, Shastri A
Best Pract Res Clin Haematol 2023 Dec;36(4):101521. Epub 2023 Oct 20 doi: 10.1016/j.beha.2023.101521. PMID: 38092478
West RR, Bauer TR, Tuschong LM, Embree LJ, Calvo KR, Tillo D, Davis J, Holland SM, Hickstein DD
Blood Adv 2023 Oct 24;7(20):6351-6363. doi: 10.1182/bloodadvances.2023010458. PMID: 37595058Free PMC Article
Durkee-Shock J, Zhang A, Liang H, Wright H, Magnusson J, Garabedian E, Marsh RA, Sullivan KE, Keller MD; USIDNET Consortium
J Allergy Clin Immunol Pract 2022 May;10(5):1334-1341.e6. Epub 2022 Feb 13 doi: 10.1016/j.jaip.2022.01.042. PMID: 35172220
Magg T, Schober T, Walz C, Ley-Zaporozhan J, Facchetti F, Klein C, Hauck F
Front Immunol 2018;9:368. Epub 2018 Feb 27 doi: 10.3389/fimmu.2018.00368. PMID: 29535735Free PMC Article
Jelkmann W
Methods Enzymol 2007;435:179-97. doi: 10.1016/S0076-6879(07)35010-6. PMID: 17998055

Prognosis

Desai SR, Chakraborty S, Shastri A
Best Pract Res Clin Haematol 2023 Dec;36(4):101521. Epub 2023 Oct 20 doi: 10.1016/j.beha.2023.101521. PMID: 38092478
Kotmayer L, Romero-Moya D, Marin-Bejar O, Kozyra E, Català A, Bigas A, Wlodarski MW, Bödör C, Giorgetti A
Br J Haematol 2022 Nov;199(4):482-495. Epub 2022 Jun 26 doi: 10.1111/bjh.18330. PMID: 35753998Free PMC Article
Sahoo SS, Kozyra EJ, Wlodarski MW
Best Pract Res Clin Haematol 2020 Sep;33(3):101197. Epub 2020 Jul 29 doi: 10.1016/j.beha.2020.101197. PMID: 33038986Free PMC Article
Amarnani AA, Poladian KR, Marciano BE, Daub JR, Williams SG, Livinski AA, Hsu AP, Palmer CL, Kenney CM, Avila DN, Holland SM, Katz JD
Sci Rep 2020 May 20;10(1):8305. doi: 10.1038/s41598-020-64852-1. PMID: 32433473Free PMC Article
Bigley V, Cytlak U, Collin M
Semin Cell Dev Biol 2019 Feb;86:50-61. Epub 2018 Feb 23 doi: 10.1016/j.semcdb.2018.02.020. PMID: 29452225

Clinical prediction guides

Kotmayer L, Romero-Moya D, Marin-Bejar O, Kozyra E, Català A, Bigas A, Wlodarski MW, Bödör C, Giorgetti A
Br J Haematol 2022 Nov;199(4):482-495. Epub 2022 Jun 26 doi: 10.1111/bjh.18330. PMID: 35753998Free PMC Article
Marciano BE, Olivier KN, Folio LR, Zerbe CS, Hsu AP, Freeman AF, Filie AC, Spinner MA, Sanchez LA, Lovell JP, Parta M, Cuellar-Rodriguez JM, Hickstein DD, Holland SM
Chest 2021 Oct;160(4):1350-1359. Epub 2021 Jun 3 doi: 10.1016/j.chest.2021.05.046. PMID: 34089740Free PMC Article
Sahoo SS, Kozyra EJ, Wlodarski MW
Best Pract Res Clin Haematol 2020 Sep;33(3):101197. Epub 2020 Jul 29 doi: 10.1016/j.beha.2020.101197. PMID: 33038986Free PMC Article
Mangaonkar AA, Patnaik MM
Mayo Clin Proc 2020 Jul;95(7):1482-1498. Epub 2020 Jun 19 doi: 10.1016/j.mayocp.2019.12.013. PMID: 32571604
Bigley V, Cytlak U, Collin M
Semin Cell Dev Biol 2019 Feb;86:50-61. Epub 2018 Feb 23 doi: 10.1016/j.semcdb.2018.02.020. PMID: 29452225

Recent systematic reviews

Ziaei H, Tonkaboni A, Shamshiri A, Rezaei N
Clin Immunol 2021 Aug;229:108796. Epub 2021 Jul 14 doi: 10.1016/j.clim.2021.108796. PMID: 34271191
Johnson JA, Yu SS, Elist M, Arkfeld D, Panush RS
Clin Rheumatol 2015 Sep;34(9):1643-5. Epub 2015 Mar 5 doi: 10.1007/s10067-015-2905-2. PMID: 25739845

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