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Immunodeficiency 66(IMD66)

MedGen UID:
1717128
Concept ID:
C5394265
Disease or Syndrome
Synonyms: IMD66; IMMUNODEFICIENCY 66
 
Gene (location): MRTFA (22q13.1-13.2)
 
Monarch Initiative: MONDO:0030013
OMIM®: 618847

Definition

Immunodeficiency-66 (IMD66) is an autosomal recessive primary immune disorder caused by defective immune cell migration and chemotaxis resulting from defects in cytoskeletal actin dynamics. Neutrophils are primarily affected, although there may be defects in dendritic cells and T and B cells. The phenotype is characterized by onset of recurrent bacterial infections in infancy. Laboratory studies show normal levels of myeloid and lymphoid cells, but there may be mild thrombocytopenia (summary by Record et al., 2015). [from OMIM]

Clinical features

From HPO
Otitis externa
MedGen UID:
10505
Concept ID:
C0029878
Disease or Syndrome
Inflammation or infection of the external auditory canal (EAC), the auricle, or both.
Meningitis
MedGen UID:
6298
Concept ID:
C0025289
Disease or Syndrome
Inflammation of the meninges.
Sepsis
MedGen UID:
48626
Concept ID:
C0036690
Disease or Syndrome
Systemic inflammatory response to infection.
Pustule
MedGen UID:
488804
Concept ID:
C0241157
Finding
A small elevation of the skin containing cloudy or purulent material usually consisting of necrotic inflammatory cells.
Recurrent skin infections
MedGen UID:
377848
Concept ID:
C1853193
Disease or Syndrome
Infections of the skin that happen multiple times.
Defective T cell proliferation
MedGen UID:
868165
Concept ID:
C4022557
Cell or Molecular Dysfunction
A reduced ability of a T cell population to expand by cell division following T cell activation.

Professional guidelines

PubMed

Böhm S, Wustrau K, Pachlopnik Schmid J, Prader S, Ahlmann M, Yacobovich J, Beier R, Speckmann C, Behnisch W, Ifversen M, Jordan M, Marsh R, Naumann-Bartsch N, Mauz-Körholz C, Hönig M, Schulz A, Malinowska I, Hines M, Nichols KE, Gil-Herrera J, Talano JA, Crooks B, Formankova R, Jorch N, Bakhtiar S, Kühnle I, Streiter M, Nathrath M, Russo A, Dürken M, Lang P, Lindemans C, Henter JI, Lehmberg K, Ehl S
Blood 2024 Mar 7;143(10):872-881. doi: 10.1182/blood.2023022281. PMID: 37992218
Phanuphak N, Seekaew P, Phanuphak P
Lancet HIV 2019 Oct;6(10):e715-e722. Epub 2019 Sep 9 doi: 10.1016/S2352-3018(19)30236-X. PMID: 31515166
Taki M, Miah T, Secord E
Pediatr Clin North Am 2019 Oct;66(5):913-923. doi: 10.1016/j.pcl.2019.06.007. PMID: 31466681

Recent clinical studies

Etiology

Pashangzadeh S, Delavari S, Moeini Shad T, Salami F, Rasouli SE, Yazdani R, Mahdaviani SA, Nabavi M, Aleyasin S, Ahanchian H, Jabbari-Azad F, Chavoshzadeh Z, Nazari F, Momen T, Sherkat R, Abolnezhadian F, Esmaeilzadeh H, Fallahpour M, Arshi S, Bemanian MH, Shokri S, Ebrahimi SS, Abolmolouki M, Farid AS, Rezaei A, Esmaeili M, Kalantari A, Sadeghi-Shabestari M, Shirkani A, Behniafard N, Khalili A, Eslamian MH, Cheraghi T, Shafie A, Tavakol M, Khoshkhui M, Iranparast S, Shamshiri M, Shahri MA, Khazaei R, Asadi M, Babaha F, Aghamohammadi A, Rezaei N, Abolhassani H
J Investig Allergol Clin Immunol 2024 Jul;34(4):233-245. doi: 10.18176/jiaci.0902. PMID: 39077769
Oertel FC, Sotirchos ES, Zimmermann HG, Motamedi S, Specovius S, Asseyer ES, Chien C, Cook L, Vasileiou E, Filippatou A, Calabresi PA, Saidha S, Pandit L, D'Cunha A, Outteryck O, Zéphir H, Pittock S, Flanagan EP, Bhatti MT, Rommer PS, Bsteh G, Zrzavy T, Kuempfel T, Aktas O, Ringelstein M, Albrecht P, Ayzenberg I, Pakeerathan T, Knier B, Aly L, Asgari N, Soelberg K, Marignier R, Tilikete CF, Cobo Calvo A, Villoslada P, Sanchez-Dalmau B, Martinez-Lapiscina EH, Llufriu S, Green AJ, Yeaman MR, Smith TJ, Brandt AU, Chen J, Paul F, Havla J; with the GJCF International Clinical Consortium for NMOSD and the CROCTINO study group
Ann Neurol 2022 Sep;92(3):476-485. Epub 2022 Jul 16 doi: 10.1002/ana.26440. PMID: 35703428
Bosworth RJ, Borschmann R, Altice FL, Kinner SA, Dolan K, Farrell M
Int J Prison Health 2022 Jan 25;18(1):66-82. Epub 2021 Aug 13 doi: 10.1108/IJPH-02-2021-0018. PMID: 35401772Free PMC Article
Milota T, Strizova Z, Smetanova J, Sediva A
Curr Opin Allergy Clin Immunol 2021 Dec 1;21(6):545-552. doi: 10.1097/ACI.0000000000000788. PMID: 34545040
Hussein K, Rath B, Ludewig B, Kreipe H, Jonigk D
Eur J Cancer 2014 Sep;50(14):2417-24. Epub 2014 Jul 11 doi: 10.1016/j.ejca.2014.06.006. PMID: 25027306

Diagnosis

Fazlollahi MR, Hamidieh AA, Moradi L, Shokouhi Shoormati R, Sabetkish N, Esmaeili B, Badalzadeh M, Alizadeh Z, Shamlou S, Movahedi M, Mahloujirad M, Razaghian A, Arshi S, Gharagozlou M, Kalantari A, Bemanian MH, Safari M, Heidarzadeh Arani M, Nabavi M, Parvaneh N, Sadeghi-Shabestari M, Behfar M, Behniafard N, Sherkat R, Ahmadian Heris J, Shariat M, Radmehr R, Houshmand M, Kazemnejad A, Molitor A, Carapito R, Bahram S, Pourpak Z, Moin M
Pediatr Allergy Immunol 2023 Jul;34(7):e13990. doi: 10.1111/pai.13990. PMID: 37492921
Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T, Cunningham-Rundles C, Etzioni A, Franco JL, Holland SM, Klein C, Morio T, Ochs HD, Oksenhendler E, Puck J, Torgerson TR, Casanova JL, Sullivan KE, Tangye SG
J Clin Immunol 2020 Jan;40(1):66-81. Epub 2020 Feb 11 doi: 10.1007/s10875-020-00758-x. PMID: 32048120Free PMC Article
Taki M, Miah T, Secord E
Pediatr Clin North Am 2019 Oct;66(5):913-923. doi: 10.1016/j.pcl.2019.06.007. PMID: 31466681
El-Bohy M, Poowuttikul P, Secord E
Pediatr Clin North Am 2019 Oct;66(5):897-903. doi: 10.1016/j.pcl.2019.06.010. PMID: 31466679
McDonnell M, Kessenich CR
Lippincotts Prim Care Pract 2000 Jan-Feb;4(1):66-73. PMID: 11022520

Therapy

Marzinke MA, Hanscom B, Wang Z, Safren SA, Psaros C, Donnell D, Richardson PA, Sullivan P, Eshleman SH, Jennings A, Feliciano KG, Jalil E, Coutinho C, Cardozo N, Maia B, Khan T, Singh Y, Middelkoop K, Franks J, Valencia J, Sanchez N, Lucas J, Rooney JF, Rinehart AR, Ford S, Adeyeye A, Cohen MS, McCauley M, Landovitz RJ, Grinsztejn B; HPTN 083 study group
Lancet HIV 2023 Nov;10(11):e703-e712. Epub 2023 Sep 29 doi: 10.1016/S2352-3018(23)00200-X. PMID: 37783219Free PMC Article
Holma P, Pesonen P, Karjalainen MK, Järvelin MR, Väyrynen S, Sliz E, Heikkilä A, Seppänen MRJ, Kettunen J, Auvinen J, Hautala T
EBioMedicine 2023 Aug;94:104712. Epub 2023 Jul 13 doi: 10.1016/j.ebiom.2023.104712. PMID: 37453363Free PMC Article
Pettit AC, Phillips PPJ, Kurbatova E, Vernon A, Nahid P, Dawson R, Dooley KE, Sanne I, Waja Z, Mohapi L, Podany AT, Samaneka W, Savic RM, Johnson JL, Muzanyi G, Lalloo UG, Bryant K, Sizemore E, Scott N, Dorman SE, Chaisson RE, Swindells S; Tuberculosis Trials Consortium (TBTC) Study 31/AIDS Clinical Trials Group (ACTG) A5349 study team
Clin Infect Dis 2023 Feb 8;76(3):e580-e589. doi: 10.1093/cid/ciac707. PMID: 36041016Free PMC Article
Milota T, Strizova Z, Smetanova J, Sediva A
Curr Opin Allergy Clin Immunol 2021 Dec 1;21(6):545-552. doi: 10.1097/ACI.0000000000000788. PMID: 34545040
Axelrod H, Adams M
Pediatr Clin North Am 2019 Oct;66(5):1007-1020. Epub 2019 Aug 5 doi: 10.1016/j.pcl.2019.06.009. PMID: 31466676

Prognosis

Jin F, Vajdic CM, Poynten IM, McGee-Avila JK, Castle PE, Grulich AE
Lancet Oncol 2024 Jul;25(7):933-944. doi: 10.1016/S1470-2045(24)00189-X. PMID: 38936380Free PMC Article
Artenie A, Stone J, Fraser H, Stewart D, Arum C, Lim AG, McNaughton AL, Trickey A, Ward Z, Abramovitz D, Alary M, Astemborski J, Bruneau J, Clipman SJ, Coffin CS, Croxford S, DeBeck K, Emanuel E, Hayashi K, Hermez JG, Low-Beer D, Luhmann N, Macphail G, Maher L, Palmateer NE, Patel EU, Sacks-Davis R, Van Den Boom W, van Santen DK, Walker JG, Hickman M, Vickerman P; HIV and HCV Incidence Review Collaborative Group
Lancet Gastroenterol Hepatol 2023 Jun;8(6):533-552. Epub 2023 Mar 27 doi: 10.1016/S2468-1253(23)00018-3. PMID: 36996853Free PMC Article
Wei F, Goodman MT, Xia N, Zhang J, Giuliano AR, D'Souza G, Hessol NA, Schim van der Loeff MF, Dai J, Neukam K, de Pokomandy A, Poynten IM, Geskus RB, Burgos J, Etienney I, Moscicki AB, Donà MG, Gillison ML, Nyitray AG, Nowak RG, Yunihastuti E, Zou H, Hidalgo-Tenorio C, Phanuphak N, Molina JM, Schofield AM, Kerr S, Fan S, Lu Y, Ong JJ, Chikandiwa AT, Teeraananchai S, Squillace N, Wiley DJ, Palefsky JM, Georges D, Alberts CJ, Clifford GM
Clin Infect Dis 2023 Feb 8;76(3):e692-e701. doi: 10.1093/cid/ciac581. PMID: 35869839Free PMC Article
Ollech A, Mashiah J, Lev A, Simon AJ, Somech R, Adam E, Barzilai A, Hagin D, Greenberger S
J Dermatol 2021 Sep;48(9):1386-1393. Epub 2021 May 27 doi: 10.1111/1346-8138.15955. PMID: 34043252
Prasad VK, Kurtzberg J
Bone Marrow Transplant 2009 Nov;44(10):643-51. Epub 2009 Oct 5 doi: 10.1038/bmt.2009.290. PMID: 19802020

Clinical prediction guides

Correa-Jimenez O, Restrepo-Gualteros S, Nino G, Cunningham-Rundles C, Sullivan KE, Fuleihan RL, Gutierrez MJ
J Clin Immunol 2023 Nov;43(8):2208-2220. Epub 2023 Nov 7 doi: 10.1007/s10875-023-01593-6. PMID: 37932514Free PMC Article
Zhao Q, Li NN, Chen YX, Zhao XY
Front Cell Infect Microbiol 2023;13:1107237. Epub 2023 May 26 doi: 10.3389/fcimb.2023.1107237. PMID: 37305416Free PMC Article
Geier CB, Ellison M, Cruz R, Pawar S, Leiss-Piller A, Zmajkovicova K, McNulty SM, Yilmaz M, Evans MO 2nd, Gordon S, Ujhazi B, Wiest I, Abolhassani H, Aghamohammadi A, Barmettler S, Bhar S, Bondarenko A, Bolyard AA, Buchbinder D, Cada M, Cavieres M, Connelly JA, Dale DC, Deordieva E, Dorsey MJ, Drysdale SB, Ehl S, Elfeky R, Fioredda F, Firkin F, Förster-Waldl E, Geng B, Goda V, Gonzalez-Granado L, Grunebaum E, Grzesk E, Henrickson SE, Hilfanova A, Hiwatari M, Imai C, Ip W, Jyonouchi S, Kanegane H, Kawahara Y, Khojah AM, Kim VH, Kojić M, Kołtan S, Krivan G, Langguth D, Lau YL, Leung D, Miano M, Mersyanova I, Mousallem T, Muskat M, Naoum FA, Noronha SA, Ouederni M, Ozono S, Richmond GW, Sakovich I, Salzer U, Schuetz C, Seeborg FO, Sharapova SO, Sockel K, Volokha A, von Bonin M, Warnatz K, Wegehaupt O, Weinberg GA, Wong KJ, Worth A, Yu H, Zharankova Y, Zhao X, Devlin L, Badarau A, Csomos K, Keszei M, Pereira J, Taveras AG, Beaussant-Cohen SL, Ong MS, Shcherbina A, Walter JE
J Clin Immunol 2022 Nov;42(8):1748-1765. Epub 2022 Aug 10 doi: 10.1007/s10875-022-01312-7. PMID: 35947323Free PMC Article
Milota T, Strizova Z, Smetanova J, Sediva A
Curr Opin Allergy Clin Immunol 2021 Dec 1;21(6):545-552. doi: 10.1097/ACI.0000000000000788. PMID: 34545040
Stiehm ER
Pediatr Res 1993 Jan;33(1 Suppl):S2-7; discussion S7-8. doi: 10.1203/00006450-199305001-00007. PMID: 8433870

Recent systematic reviews

Wu S, Wang J, Guo Q, Lan H, Sun Y, Ren M, Liu Y, Wang P, Wang L, Su R, Zhang J, Chen Y, Li G
Clin Microbiol Infect 2023 Aug;29(8):1000-1007. Epub 2023 Mar 13 doi: 10.1016/j.cmi.2023.03.002. PMID: 36921717
Kay AW, Ness T, Verkuijl SE, Viney K, Brands A, Masini T, González Fernández L, Eisenhut M, Detjen AK, Mandalakas AM, Steingart KR, Takwoingi Y
Cochrane Database Syst Rev 2022 Sep 6;9(9):CD013359. doi: 10.1002/14651858.CD013359.pub3. PMID: 36065889Free 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
Stelzle D, Tanaka LF, Lee KK, Ibrahim Khalil A, Baussano I, Shah ASV, McAllister DA, Gottlieb SL, Klug SJ, Winkler AS, Bray F, Baggaley R, Clifford GM, Broutet N, Dalal S
Lancet Glob Health 2021 Feb;9(2):e161-e169. Epub 2020 Nov 16 doi: 10.1016/S2214-109X(20)30459-9. PMID: 33212031Free PMC Article
James C, Harfouche M, Welton NJ, Turner KM, Abu-Raddad LJ, Gottlieb SL, Looker KJ
Bull World Health Organ 2020 May 1;98(5):315-329. Epub 2020 Mar 25 doi: 10.2471/BLT.19.237149. PMID: 32514197Free PMC Article

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