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Immunodeficiency 112(IMD112)

MedGen UID:
1841269
Concept ID:
C5830633
Disease or Syndrome
Synonym: IMD112
 
Gene (location): MAP3K14 (17q21.31)
 
Monarch Initiative: MONDO:0957535
OMIM®: 620449

Definition

Immunodeficiency-112 (IMD112) is an autosomal recessive primary immunologic disorder with variable manifestations beginning in early childhood. Some patients have recurrent bacterial, viral, and fungal infections, including disseminated bacillus Calmette-Guerin (BCG)-related infections, whereas at least 1 patient only presented with BCG-related infections. Immunologic workup shows variable abnormalities affecting lymphoid immunity, including hypogammaglobulinemia, lymphopenia or paradoxical lymphocytosis, and defects in B, T, and NK cell differentiation and function mainly due to disruption of the noncanonical NFKB (see 164011) signaling pathway (Willmann et al., 2014; Schlechter et al., 2017). [from OMIM]

Clinical features

From HPO
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Recurrent lower respiratory tract infections
MedGen UID:
756211
Concept ID:
C3163798
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
Chronic mucocutaneous candidiasis
MedGen UID:
2426
Concept ID:
C0006845
Disease or Syndrome
Recurrent or persistent superficial Candida infections of the skin, mucous membranes, and nails.
Decreased circulating IgA concentration
MedGen UID:
57934
Concept ID:
C0162538
Disease or Syndrome
Decreased levels of immunoglobulin A (IgA).
Decreased circulating total IgM
MedGen UID:
116095
Concept ID:
C0239989
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
Recurrent viral infections
MedGen UID:
332357
Concept ID:
C1837066
Finding
Increased susceptibility to viral infections, as manifested by recurrent episodes of viral infection.
Recurrent bacterial infections
MedGen UID:
334943
Concept ID:
C1844383
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial 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.
Increased B cell count
MedGen UID:
349067
Concept ID:
C1858972
Finding
An abnormal increase from the normal count of B cells.
T lymphocytopenia
MedGen UID:
419385
Concept ID:
C2931322
Finding
An abnormally low count of T cells.
BCGosis
MedGen UID:
823215
Concept ID:
C3830467
Disease or Syndrome
Distant, or disseminated infection with Bacillus Calmette-Guerin (BCG) following vaccination associated with failure to contain thebacillus Calmette-Guerin (BCG) following vaccination leading to spread of BCG to many sites in the body. The tuberculosis vaccine BCG contains live attenuated Mycobacterium bovis.
Increased T cell count
MedGen UID:
867575
Concept ID:
C4021960
Finding
An abnormal increase in the total number of T cells detected in the blood.
Decreased proportion of class-switched memory B cells
MedGen UID:
892709
Concept ID:
C4072925
Finding
A reduction in the normal proportion of class-switched memory B cells (CD19+/CD27+/IgM+/IgD+) relative to the total number of B cells. Marginal zone B cells undergo limited somatic hypermutation and produce high-affinity IgM and some IgG, whereas class-switched memory B cells synthetize IgG, IgM, and IgA.
BCGitis
MedGen UID:
1684722
Concept ID:
C5139070
Disease or Syndrome
Local or regional infection with Bacillus Calmette-Guerin (BCG) following vaccination.
Decreased circulating IgG concentration
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Decreased proportion of gamma-delta T cells
MedGen UID:
1713360
Concept ID:
C5398020
Finding
Decreased proportion of gamma-delta T cells relative to the total number of T cells.

Professional guidelines

PubMed

Yadav RM, Gupta M, Dalvi A, Bargir UA, Hule G, Shabrish S, Aluri J, Kulkarni M, Kambli P, Uppuluri R, Seshadri S, Jagadeesh S, Suresh B, Raja J, Taur P, Malaischamy S, Ghosh P, Mahalingam S, Kadam P, Lashkari HP, Tamhankar P, Tamhankar V, Mithbawkar S, Bhattad S, Jhawar P, Makam A, Bansal V, Prasad M, Govindaraj G, Guhan B, Bharadwaj Tallapaka K, Desai M, Raj R, Madkaikar MR
Front Immunol 2020;11:612316. Epub 2020 Dec 7 doi: 10.3389/fimmu.2020.612316. PMID: 33365035Free PMC Article
Mikkelsen E, Hontelez JAC, Nonvignon J, Amon S, Asante FA, Aikins MK, van de Haterd J, Baltussen R
AIDS 2017 Oct 23;31(16):2279-2286. doi: 10.1097/QAD.0000000000001612. PMID: 28991025Free PMC Article
Ochs HD, Hagin D
Ann Allergy Asthma Immunol 2014 Jun;112(6):489-95. doi: 10.1016/j.anai.2014.04.007. PMID: 24860921

Recent clinical studies

Etiology

Rajasingham R, Govender NP, Jordan A, Loyse A, Shroufi A, Denning DW, Meya DB, Chiller TM, Boulware DR
Lancet Infect Dis 2022 Dec;22(12):1748-1755. Epub 2022 Aug 29 doi: 10.1016/S1473-3099(22)00499-6. PMID: 36049486Free PMC Article
Hyatt AN, Lake JE
Curr HIV/AIDS Rep 2022 Oct;19(5):415-424. Epub 2022 Aug 13 doi: 10.1007/s11904-022-00620-2. PMID: 35962851
Onwubiko UN, Yoon JC, Ajoku S, Khan AN, Holland DP
Am J Public Health 2022 Jun;112(6):881-885. Epub 2022 Apr 14 doi: 10.2105/AJPH.2022.306801. PMID: 35420895Free PMC Article
Sousa JD, Müller V, Vandamme AM
Viruses 2022 Mar 5;14(3) doi: 10.3390/v14030538. PMID: 35336945Free PMC Article
Hsue PY, Waters DD
Circulation 2005 Dec 20;112(25):3947-57. doi: 10.1161/CIRCULATIONAHA.105.546465. PMID: 16365213

Diagnosis

Rajasingham R, Govender NP, Jordan A, Loyse A, Shroufi A, Denning DW, Meya DB, Chiller TM, Boulware DR
Lancet Infect Dis 2022 Dec;22(12):1748-1755. Epub 2022 Aug 29 doi: 10.1016/S1473-3099(22)00499-6. PMID: 36049486Free PMC Article
Onwubiko UN, Yoon JC, Ajoku S, Khan AN, Holland DP
Am J Public Health 2022 Jun;112(6):881-885. Epub 2022 Apr 14 doi: 10.2105/AJPH.2022.306801. PMID: 35420895Free PMC Article
Ochs HD, Hagin D
Ann Allergy Asthma Immunol 2014 Jun;112(6):489-95. doi: 10.1016/j.anai.2014.04.007. PMID: 24860921
Marc T, Kevin R
Handb Clin Neurol 2013;112:1219-27. doi: 10.1016/B978-0-444-52910-7.00044-1. PMID: 23622332
Friedman-Kien AE
Recent Results Cancer Res 1988;112:27-36. PMID: 3060917

Therapy

Teixeira LAA, Santos B, Correia MG, Valiquette C, Bastos ML, Menzies D, Trajman A
Clin Infect Dis 2024 May 15;78(5):1321-1327. doi: 10.1093/cid/ciae101. PMID: 38407417
Cheng LL, Guan WJ, Duan CY, Zhang NF, Lei CL, Hu Y, Chen AL, Li SY, Zhuo C, Deng XL, Cheng FJ, Gao Y, Zhang JH, Xie JX, Peng H, Li YX, Wu XX, Liu W, Peng H, Wang J, Xiao GM, Chen PY, Wang CY, Yang ZF, Zhao JC, Zhong NS
JAMA Intern Med 2021 Jan 1;181(1):71-78. doi: 10.1001/jamainternmed.2020.5503. PMID: 32910179Free PMC Article
Hsue PY, Waters DD
Circulation 2005 Dec 20;112(25):3947-57. doi: 10.1161/CIRCULATIONAHA.105.546465. PMID: 16365213
Berger M
Clin Immunol 2004 Jul;112(1):1-7. doi: 10.1016/j.clim.2004.02.002. PMID: 15207776
Exner R, Wessner B, Manhart N, Roth E
Wien Klin Wochenschr 2000 Jul 28;112(14):610-6. PMID: 11008322

Prognosis

Teixeira LAA, Santos B, Correia MG, Valiquette C, Bastos ML, Menzies D, Trajman A
Clin Infect Dis 2024 May 15;78(5):1321-1327. doi: 10.1093/cid/ciae101. PMID: 38407417
Li T, Zheng F, Cheng F
Int Immunopharmacol 2022 Nov;112:109277. Epub 2022 Sep 27 doi: 10.1016/j.intimp.2022.109277. PMID: 36206651Free PMC Article
Cheng LL, Guan WJ, Duan CY, Zhang NF, Lei CL, Hu Y, Chen AL, Li SY, Zhuo C, Deng XL, Cheng FJ, Gao Y, Zhang JH, Xie JX, Peng H, Li YX, Wu XX, Liu W, Peng H, Wang J, Xiao GM, Chen PY, Wang CY, Yang ZF, Zhao JC, Zhong NS
JAMA Intern Med 2021 Jan 1;181(1):71-78. doi: 10.1001/jamainternmed.2020.5503. PMID: 32910179Free PMC Article
Jansen A, van Deuren M, Miller J, Litzman J, de Gracia J, Sáenz-Cuesta M, Szaflarska A, Martelius T, Takiguchi Y, Patel S, Misbah S, Simon A; Good syndrome Study Group
Clin Immunol 2016 Oct;171:12-17. Epub 2016 Aug 4 doi: 10.1016/j.clim.2016.07.025. PMID: 27497628
LeBien TW, Tedder TF
Blood 2008 Sep 1;112(5):1570-80. doi: 10.1182/blood-2008-02-078071. PMID: 18725575Free PMC Article

Clinical prediction guides

Huang KY, Kao HJ, Weng TH, Chen CH, Weng SL
Brief Bioinform 2022 Nov 19;23(6) doi: 10.1093/bib/bbac406. PMID: 36215051
Sousa JD, Müller V, Vandamme AM
Viruses 2022 Mar 5;14(3) doi: 10.3390/v14030538. PMID: 35336945Free PMC Article
Conway JM, Perelson AS
Proc Natl Acad Sci U S A 2015 Apr 28;112(17):5467-72. Epub 2015 Apr 13 doi: 10.1073/pnas.1419162112. PMID: 25870266Free PMC Article
Marc T, Kevin R
Handb Clin Neurol 2013;112:1219-27. doi: 10.1016/B978-0-444-52910-7.00044-1. PMID: 23622332
LeBien TW, Tedder TF
Blood 2008 Sep 1;112(5):1570-80. doi: 10.1182/blood-2008-02-078071. PMID: 18725575Free PMC Article

Recent systematic reviews

Li J, Wei E, Reisinger A, French LE, Clanner-Engelshofen BM, Reinholz M
Dermatology 2023;239(1):12-31. Epub 2022 Oct 28 doi: 10.1159/000526296. PMID: 36310014
Eccles R, du Toit M, de Jongh G, Krüger E
Breastfeed Med 2022 Feb;17(2):112-130. Epub 2021 Dec 21 doi: 10.1089/bfm.2021.0107. PMID: 34936484
Wei F, Gaisa MM, D'Souza G, Xia N, Giuliano AR, Hawes SE, Gao L, Cheng SH, Donà MG, Goldstone SE, Schim van der Loeff MF, Neukam K, Meites E, Poynten IM, Dai J, Combes JD, Wieland U, Burgos J, Wilkin TJ, Hernandez AL, Iribarren Díaz M, Hidalgo-Tenorio C, Valencia Arredondo M, Nyitray AG, Wentzensen N, Chow EP, Smelov V, Nowak RG, Phanuphak N, Woo YL, Choi Y, Hu Y, Schofield AM, Woestenberg PJ, Chikandiwa AT, Hickey AC, de Pokomandy A, Murenzi G, Péré H, Del Pino M, Ortiz AP, Charnot-Katsikas A, Liu X, Chariyalertsak S, Strong C, Ong JJ, Yunihastuti E, Etienney I, Ferré VM, Zou H, Segondy M, Chinyowa S, Alberts CJ, Clifford GM
Lancet HIV 2021 Sep;8(9):e531-e543. Epub 2021 Jul 30 doi: 10.1016/S2352-3018(21)00108-9. PMID: 34339628Free PMC Article
Santana LM, Valadares EA, Ferreira-Júnior CU, Santos MF, Albergaria BH, Rosa-Júnior M
AIDS Rev 2020 Jul 8;22(2):112-122. doi: 10.24875/AIDSRev.20000132. PMID: 32180590
Ford N, Calmy A, Andrieux-Meyer I, Hargreaves S, Mills EJ, Shubber Z
AIDS 2013 Apr 24;27(7):1135-43. doi: 10.1097/QAD.0b013e32835e0752. PMID: 23299174

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