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Immunodeficiency 77(IMD77)

MedGen UID:
1788976
Concept ID:
C5543173
Disease or Syndrome
Synonyms: IMD77; IMMUNODEFICIENCY 77
 
Gene (location): MPEG1 (11q12.1)
 
Monarch Initiative: MONDO:0030973
OMIM®: 619223

Definition

Immunodeficiency-77 (IMD77) is an immunologic disorder characterized by recurrent and persistent polymicrobial infections with multiple unusual organisms. Skin and pulmonary infections are the most common, consistent with increased susceptibility to epithelial cell infections. The age at onset is highly variable: some patients have recurrent infections from childhood, whereas others present in late adulthood. The limited number of reported patients are all female, suggesting incomplete penetrance or a possible sex-influenced trait. Patient cells, mainly macrophages, show impaired killing of intracellular bacteria and organisms, including nontubercular mycobacteria, although there is also impaired killing of other organisms, such as Pseudomonas, Candida, and Aspergillus. Treatment with gamma-IFN (IFNG; 147570) may be a therapeutic option (summary by McCormack et al., 2017 and Merselis et al., 2020). [from OMIM]

Clinical features

From HPO
Gastroparesis
MedGen UID:
101809
Concept ID:
C0152020
Disease or Syndrome
Decreased strength of the muscle layer of stomach, which leads to a decreased ability to empty the contents of the stomach despite the absence of obstruction.
Bilateral sensorineural hearing impairment
MedGen UID:
96788
Concept ID:
C0452138
Disease or Syndrome
A bilateral form of sensorineural hearing impairment.
Cellulitis
MedGen UID:
40174
Concept ID:
C0007642
Disease or Syndrome
A bacterial infection and inflammation of the skin und subcutaneous tissues.
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.
Chronic obstructive pulmonary disease
MedGen UID:
9818
Concept ID:
C0024117
Disease or Syndrome
Chronic obstructive pulmonary disease (COPD) is a common, complex disorder associated with substantial morbidity and mortality. COPD is defined by irreversible airflow obstruction due to chronic bronchitis, emphysema, and/or small airways disease. Airflow obstruction is typically determined by reductions in quantitative spirometric indices, including forced expiratory volume at 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) (Silverman et al., 2002; Celedon et al., 2004).
Cutaneous abscess
MedGen UID:
450991
Concept ID:
C0149777
Pathologic Function
A circumscribed area of pus or necrotic debris in the skin.
Recurrent tonsillitis
MedGen UID:
1781351
Concept ID:
C0740402
Disease or Syndrome
Inflammation of the tonsils that has occurred repeatedly. The definition of recurrent may vary somewhat, but the criteria used recently as a measure of severity were five or more episodes of true tonsillitis per year, symptoms recurring for at least a year, and episodes that are disabling and that prevent normal functioning. In some cases recurrent tonsillitis may be related to immunosusceptibility. Evidence exists for a genetic predisposition for recurrent tonsillitis.
Nontuberculous mycobacterial pulmonary infection
MedGen UID:
1700174
Concept ID:
C5139228
Disease or Syndrome
An infection of the lung caused by environmental mycobacteria. Such infections can occur in individuals with predisposing lung disease or immune disease.

Professional guidelines

PubMed

Weigel R, Phiri S, Chiputula F, Gumulira J, Brinkhof M, Gsponer T, Tweya H, Egger M, Keiser O
Trop Med Int Health 2010 Aug;15(8):934-44. Epub 2010 Jun 15 doi: 10.1111/j.1365-3156.2010.02561.x. PMID: 20561308Free PMC Article

Recent clinical studies

Etiology

Jarrín I, Rava M, Del Romero Raposo J, Rivero A, Del Romero Guerrero J, De Lagarde M, Martínez Sanz J, Navarro G, Dalmau D, Blanco JR, Koerting A, Gomez Castell J, Del Amo J; CoRIS
AIDS 2024 Mar 1;38(3):387-395. Epub 2023 Oct 27 doi: 10.1097/QAD.0000000000003772. PMID: 37905999
Asgardoon MH, Azizi G, Yazdani R, Sohani M, Pashangzadeh S, Kalantari A, Shariat M, Shafiei A, Salami F, Jamee M, Rasouli SE, Mohammadi J, Hassanpour G, Tavakol M, Chavoshzadeh Z, Mahdaviani SA, Momen T, Behniafard N, Nabavi M, Bemanian MH, Arshi S, Molatefi R, Sherkat R, Shirkani A, Alyasin S, Jabbari-Azad F, Ghaffari J, Mesdaghi M, Ahanchian H, Khoshkhui M, Eslamian MH, Cheraghi T, Dabbaghzadeh A, Nasiri Kalmarzi R, Esmaeilzadeh H, Tafaroji J, Khalili A, Sadeghi-Shabestari M, Darougar S, Moghtaderi M, Ahmadiafshar A, Shakerian B, Heidarzadeh M, Ghalebaghi B, Fathi SM, Darabi B, Fallahpour M, Mohsenzadeh A, Ebrahimi S, Sharafian S, Vosughimotlagh A, Tafakoridelbari M, Rahimi Haji-Abadi M, Ashournia P, Razaghian A, Rezaei A, Delavari S, Shirmast P, Babaha F, Samavat A, Mamishi S, Khazaei HA, Negahdari B, Rezaei N, Abolhassani H, Aghamohammadi A
Int Arch Allergy Immunol 2020;181(9):706-714. Epub 2020 Jul 2 doi: 10.1159/000508817. PMID: 32615565
Tallar M, Routes J
Clin Perinatol 2020 Mar;47(1):77-86. Epub 2019 Sep 27 doi: 10.1016/j.clp.2019.09.004. PMID: 32000930
Al-Herz W, Aldhekri H, Barbouche MR, Rezaei N
Hum Hered 2014;77(1-4):138-43. Epub 2014 Jul 29 doi: 10.1159/000357710. PMID: 25060276
Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, Vlkova M, Hernandez M, Detkova D, Bos PR, Poerksen G, von Bernuth H, Baumann U, Goldacker S, Gutenberger S, Schlesier M, Bergeron-van der Cruyssen F, Le Garff M, Debré P, Jacobs R, Jones J, Bateman E, Litzman J, van Hagen PM, Plebani A, Schmidt RE, Thon V, Quinti I, Espanol T, Webster AD, Chapel H, Vihinen M, Oksenhendler E, Peter HH, Warnatz K
Blood 2008 Jan 1;111(1):77-85. Epub 2007 Sep 26 doi: 10.1182/blood-2007-06-091744. PMID: 17898316

Diagnosis

Dzhus M, Ehlers L, Wouters M, Jansen K, Schrijvers R, De Somer L, Vanderschueren S, Baggio M, Moens L, Verhaaren B, Lories R, Bucciol G, Meyts I
J Clin Immunol 2023 Nov;43(8):1916-1926. Epub 2023 Aug 7 doi: 10.1007/s10875-023-01555-y. PMID: 37548813Free PMC Article
Nishimura A, Uppuluri R, Raj R, Swaminathan VV, Cheng Y, Abu-Arja RF, Fu B, Laberko A, Albert MH, Hauck F, Bucciol G, Bigley V, Elcombe S, Kharya G, Pronk CJH, Wehr C, Neven B, Warnatz K, Meyts I, Morio T, Gennery AR, Kanegane H
J Clin Immunol 2023 Nov;43(8):1827-1839. Epub 2023 Jul 16 doi: 10.1007/s10875-023-01551-2. PMID: 37454339
Tallar M, Routes J
Clin Perinatol 2020 Mar;47(1):77-86. Epub 2019 Sep 27 doi: 10.1016/j.clp.2019.09.004. PMID: 32000930
Al-Herz W, Aldhekri H, Barbouche MR, Rezaei N
Hum Hered 2014;77(1-4):138-43. Epub 2014 Jul 29 doi: 10.1159/000357710. PMID: 25060276
Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, Vlkova M, Hernandez M, Detkova D, Bos PR, Poerksen G, von Bernuth H, Baumann U, Goldacker S, Gutenberger S, Schlesier M, Bergeron-van der Cruyssen F, Le Garff M, Debré P, Jacobs R, Jones J, Bateman E, Litzman J, van Hagen PM, Plebani A, Schmidt RE, Thon V, Quinti I, Espanol T, Webster AD, Chapel H, Vihinen M, Oksenhendler E, Peter HH, Warnatz K
Blood 2008 Jan 1;111(1):77-85. Epub 2007 Sep 26 doi: 10.1182/blood-2007-06-091744. PMID: 17898316

Therapy

Pasqualotto AC, Lana DD, Godoy CSM, Leitão TDMJS, Bay MB, Damasceno LS, Soares RBA, Kist R, Silva LR, Wiltgen D, Melo M, Guimarães TF, Guimarães MR, Vechi HT, de Mesquita JRL, Monteiro GRG, Adenis A, Bahr NC, Spec A, Boulware DR, Israelski D, Chiller T, Falci DR
Clin Infect Dis 2023 Oct 13;77(8):1126-1132. doi: 10.1093/cid/ciad313. PMID: 37232940Free PMC Article
García-Blanco D, Gravier-Hernández R, Rabeiro-Martínez CL, Gil Del Valle L, Pérez-Ávila J
MEDICC Rev 2019 Apr-Jul;21(2-3):59-68. doi: 10.37757/MR2019.V21.N2-3.11. PMID: 31401638
Wedi B
Drugs Today (Barc) 2019 Jul;55(7):439-448. doi: 10.1358/dot.2019.55.7.2985293. PMID: 31347612
Lopez LM, Grey TW, Chen M, Tolley EE, Stockton LL
Cochrane Database Syst Rev 2016 Nov 23;11(11):CD007249. doi: 10.1002/14651858.CD007249.pub5. PMID: 27879980Free PMC Article
Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, Vlkova M, Hernandez M, Detkova D, Bos PR, Poerksen G, von Bernuth H, Baumann U, Goldacker S, Gutenberger S, Schlesier M, Bergeron-van der Cruyssen F, Le Garff M, Debré P, Jacobs R, Jones J, Bateman E, Litzman J, van Hagen PM, Plebani A, Schmidt RE, Thon V, Quinti I, Espanol T, Webster AD, Chapel H, Vihinen M, Oksenhendler E, Peter HH, Warnatz K
Blood 2008 Jan 1;111(1):77-85. Epub 2007 Sep 26 doi: 10.1182/blood-2007-06-091744. PMID: 17898316

Prognosis

GBD 2021 HIV Collaborators
Lancet HIV 2024 Dec;11(12):e807-e822. Epub 2024 Nov 25 doi: 10.1016/S2352-3018(24)00212-1. PMID: 39608393Free PMC Article
Wahyuningsih R, Adawiyah R, Sjam R, Prihartono J, Ayu Tri Wulandari E, Rozaliyani A, Ronny R, Imran D, Tugiran M, Siagian FE, Denning DW
Mycoses 2021 Oct;64(10):1203-1212. Epub 2021 Jun 25 doi: 10.1111/myc.13304. PMID: 33971053
Gameiro J, Agapito Fonseca J, Jorge S, Lopes JA
HIV Med 2019 Feb;20(2):77-87. Epub 2018 Nov 8 doi: 10.1111/hiv.12685. PMID: 30411475
Shah ASV, Stelzle D, Lee KK, Beck EJ, Alam S, Clifford S, Longenecker CT, Strachan F, Bagchi S, Whiteley W, Rajagopalan S, Kottilil S, Nair H, Newby DE, McAllister DA, Mills NL
Circulation 2018 Sep 11;138(11):1100-1112. doi: 10.1161/CIRCULATIONAHA.117.033369. PMID: 29967196Free PMC Article
Redd AD, Quinn TC, Tobian AA
Lancet Infect Dis 2013 Jul;13(7):622-8. Epub 2013 May 31 doi: 10.1016/S1473-3099(13)70066-5. PMID: 23726798Free PMC Article

Clinical prediction guides

Letendre SL, Chen H, McKhann A, Roa J, Vecchio A, Daar ES, Berzins B, Hunt PW, Marra CM, Campbell TB, Coombs RW, Ma Q, Swaminathan S, Macatangay BJC, Morse GD, Miller T, Rusin D, Greninger AL, Ha B, Alston-Smith B, Robertson K, Paul R, Spudich S; A5324 Study Team
Clin Infect Dis 2023 Sep 18;77(6):866-874. doi: 10.1093/cid/ciad265. PMID: 37183889Free PMC Article
Lucena LA, Dantas GBDS, Carneiro TV, Lacerda HG
Rev Soc Bras Med Trop 2023;56 Epub 2023 Jan 23 doi: 10.1590/0037-8682-0155-2022. PMID: 36700598Free PMC Article
Bakeman R
Am Psychol 2022 Feb-Mar;77(2):310. Epub 2021 Dec 23 doi: 10.1037/amp0000907. PMID: 34941312
Mukhina AA, Kuzmenko NB, Rodina YA, Kondratenko IV, Bologov AA, Latysheva TV, Prodeus AP, Pampura AN, Balashov DN, Ilyina NI, Latysheva EA, Deordieva EA, Shvets OA, Deripapa EV, Abramova IN, Pashenko OE, Vahlyarskaya SS, Zinovyeva NV, Zimin SB, Skorobogatova EV, Machneva EB, Fomina DS, Ipatova MG, Barycheva LY, Khachirova LS, Tuzankina IA, Bolkov MA, Shakhova NV, Kamaltynova EM, Sibgatullina FI, Guseva MN, Kuznetsova RN, Milichkina AM, Totolian AA, Kalinina NM, Goltsman EA, Sulima EI, Kutlyanceva AY, Moiseeva AA, Khoreva AL, Nesterenko Z, Tymofeeva EV, Ermakova A, Proligina DD, Kalmetieva LR, Davletbaieva GA, Mirsayapova IA, Richkova OA, Kuzmicheva KP, Grakhova MA, Yudina NB, Orlova EA, Selezneva OS, Piskunova SG, Samofalova TV, Bukina TV, Pechkurova AD, Migacheva N, Zhestkov A, Barmina EV, Parfenova NA, Isakova SN, Averina EV, Sazonova IV, Starikova SY, Shilova TV, Asekretova TV, Suprun RN, Kleshchenko EI, Lebedev VV, Demikhova EV, Demikhov VG, Kalinkina VA, Gorenkova AV, Duryagina SN, Pavlova TB, Shinkareva VM, Smoleva IV, Aleksandrova TP, Bambaeva ZV, Philippova MA, Gracheva EM, Tcyvkina GI, Efremenkov AV, Mashkovskaya D, Yarovaya IV, Alekseenko VA, Fisyun IV, Molokova GV, Troitskya EV, Piatkina LI, Vlasova EV, Ukhanova O, Chernishova EG, Vasilieva M, Laba OM, Volodina E, Safonova EV, Voronin KA, Gurkina MV, Rumyantsev AG, Novichkova GA, Shcherbina AY
Front Immunol 2020;11:1491. Epub 2020 Aug 6 doi: 10.3389/fimmu.2020.01491. PMID: 32849507Free PMC Article
Lima CT, Araújo PSR, Teixeira HM, Santos JBD, Silveira VMD
An Bras Dermatol 2017 Mar-Apr;92(2):172-176. doi: 10.1590/abd1806-4841.20175377. PMID: 28538874Free PMC Article

Recent systematic reviews

O Murchu E, Marshall L, Teljeur C, Harrington P, Hayes C, Moran P, Ryan M
BMJ Open 2022 May 11;12(5):e048478. doi: 10.1136/bmjopen-2020-048478. PMID: 35545381Free PMC Article
Teferi MY, El-Khatib Z, Boltena MT, Andualem AT, Asamoah BO, Biru M, Adane HT
Int J Environ Res Public Health 2021 Oct 12;18(20) doi: 10.3390/ijerph182010678. PMID: 34682420Free PMC Article
Zhou T, Guan H, Wang L, Zhang Y, Rui M, Ma A
Front Public Health 2021;9:675523. Epub 2021 Jun 29 doi: 10.3389/fpubh.2021.675523. PMID: 34268287Free PMC Article
Hemelaar J, Elangovan R, Yun J, Dickson-Tetteh L, Fleminger I, Kirtley S, Williams B, Gouws-Williams E, Ghys PD; WHO–UNAIDS Network for HIV Isolation Characterisation
Lancet Infect Dis 2019 Feb;19(2):143-155. Epub 2018 Nov 30 doi: 10.1016/S1473-3099(18)30647-9. PMID: 30509777
Shah ASV, Stelzle D, Lee KK, Beck EJ, Alam S, Clifford S, Longenecker CT, Strachan F, Bagchi S, Whiteley W, Rajagopalan S, Kottilil S, Nair H, Newby DE, McAllister DA, Mills NL
Circulation 2018 Sep 11;138(11):1100-1112. doi: 10.1161/CIRCULATIONAHA.117.033369. PMID: 29967196Free PMC Article

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