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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

Mears V, Jakubecz C, Seeco C, Woodson S, Serra A, Abboud H
J Neuroimmunol 2023 Apr 15;377:578066. Epub 2023 Mar 8 doi: 10.1016/j.jneuroim.2023.578066. PMID: 36917920
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
Tenforde MW, Shapiro AE, Rouse B, Jarvis JN, Li T, Eshun-Wilson I, Ford N
Cochrane Database Syst Rev 2018 Jul 25;7(7):CD005647. doi: 10.1002/14651858.CD005647.pub3. PMID: 30045416Free PMC Article

Recent clinical studies

Etiology

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
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
Zielen S, Duecker RP, Woelke S, Donath H, Bakhtiar S, Buecker A, Kreyenberg H, Huenecke S, Bader P, Mahlaoui N, Ehl S, El-Helou SM, Pietrucha B, Plebani A, van der Flier M, van Aerde K, Kilic SS, Reda SM, Kostyuchenko L, McDermott E, Galal N, Pignata C, Pérez JLS, Laws HJ, Niehues T, Kutukculer N, Seidel MG, Marques L, Ciznar P, Edgar JDM, Soler-Palacín P, von Bernuth H, Krueger R, Meyts I, Baumann U, Kanariou M, Grimbacher B, Hauck F, Graf D, Granado LIG, Prader S, Reisli I, Slatter M, Rodríguez-Gallego C, Arkwright PD, Bethune C, Deripapa E, Sharapova SO, Lehmberg K, Davies EG, Schuetz C, Kindle G, Schubert R
J Clin Immunol 2021 Nov;41(8):1878-1892. Epub 2021 Sep 3 doi: 10.1007/s10875-021-01090-8. PMID: 34477998Free PMC Article
Marcus JL, Leyden WA, Chao CR, Horberg MA, Klein DB, Quesenberry CP Jr, Towner WJ, Silverberg MJ
AIDS 2017 Apr 24;31(7):989-993. doi: 10.1097/QAD.0000000000001434. PMID: 28252529Free PMC Article
Stiehm ER
Pediatr Res 1993 Jan;33(1 Suppl):S2-7; discussion S7-8. doi: 10.1203/00006450-199305001-00007. PMID: 8433870

Diagnosis

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
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
Medeiros RCDSC, Medeiros JA, Silva TALD, Andrade RD, Medeiros DC, Araújo JS, Oliveira AMG, Costa MAA, Dantas PMS
Rev Saude Publica 2017 Jul 20;51:66. doi: 10.1590/S1518-8787.2017051006266. PMID: 28746573Free PMC Article
McDonnell M, Kessenich CR
Lippincotts Prim Care Pract 2000 Jan-Feb;4(1):66-73. PMID: 11022520

Therapy

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
Zielen S, Duecker RP, Woelke S, Donath H, Bakhtiar S, Buecker A, Kreyenberg H, Huenecke S, Bader P, Mahlaoui N, Ehl S, El-Helou SM, Pietrucha B, Plebani A, van der Flier M, van Aerde K, Kilic SS, Reda SM, Kostyuchenko L, McDermott E, Galal N, Pignata C, Pérez JLS, Laws HJ, Niehues T, Kutukculer N, Seidel MG, Marques L, Ciznar P, Edgar JDM, Soler-Palacín P, von Bernuth H, Krueger R, Meyts I, Baumann U, Kanariou M, Grimbacher B, Hauck F, Graf D, Granado LIG, Prader S, Reisli I, Slatter M, Rodríguez-Gallego C, Arkwright PD, Bethune C, Deripapa E, Sharapova SO, Lehmberg K, Davies EG, Schuetz C, Kindle G, Schubert R
J Clin Immunol 2021 Nov;41(8):1878-1892. Epub 2021 Sep 3 doi: 10.1007/s10875-021-01090-8. PMID: 34477998Free PMC Article
Sudfeld CR, Mugusi F, Muhihi A, Aboud S, Nagu TJ, Ulenga N, Hong B, Wang M, Fawzi WW
Lancet HIV 2020 Jul;7(7):e463-e471. doi: 10.1016/S2352-3018(20)30108-9. PMID: 32621874Free PMC Article
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

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
Zielen S, Duecker RP, Woelke S, Donath H, Bakhtiar S, Buecker A, Kreyenberg H, Huenecke S, Bader P, Mahlaoui N, Ehl S, El-Helou SM, Pietrucha B, Plebani A, van der Flier M, van Aerde K, Kilic SS, Reda SM, Kostyuchenko L, McDermott E, Galal N, Pignata C, Pérez JLS, Laws HJ, Niehues T, Kutukculer N, Seidel MG, Marques L, Ciznar P, Edgar JDM, Soler-Palacín P, von Bernuth H, Krueger R, Meyts I, Baumann U, Kanariou M, Grimbacher B, Hauck F, Graf D, Granado LIG, Prader S, Reisli I, Slatter M, Rodríguez-Gallego C, Arkwright PD, Bethune C, Deripapa E, Sharapova SO, Lehmberg K, Davies EG, Schuetz C, Kindle G, Schubert R
J Clin Immunol 2021 Nov;41(8):1878-1892. Epub 2021 Sep 3 doi: 10.1007/s10875-021-01090-8. PMID: 34477998Free PMC Article
Marcus JL, Leyden WA, Chao CR, Horberg MA, Klein DB, Quesenberry CP Jr, Towner WJ, Silverberg MJ
AIDS 2017 Apr 24;31(7):989-993. doi: 10.1097/QAD.0000000000001434. PMID: 28252529Free PMC Article
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
Harries AD
Lancet 1990 Feb 17;335(8686):387-90. doi: 10.1016/0140-6736(90)90216-r. PMID: 1968123

Clinical prediction guides

Mears V, Jakubecz C, Seeco C, Woodson S, Serra A, Abboud H
J Neuroimmunol 2023 Apr 15;377:578066. Epub 2023 Mar 8 doi: 10.1016/j.jneuroim.2023.578066. PMID: 36917920
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
Zielen S, Duecker RP, Woelke S, Donath H, Bakhtiar S, Buecker A, Kreyenberg H, Huenecke S, Bader P, Mahlaoui N, Ehl S, El-Helou SM, Pietrucha B, Plebani A, van der Flier M, van Aerde K, Kilic SS, Reda SM, Kostyuchenko L, McDermott E, Galal N, Pignata C, Pérez JLS, Laws HJ, Niehues T, Kutukculer N, Seidel MG, Marques L, Ciznar P, Edgar JDM, Soler-Palacín P, von Bernuth H, Krueger R, Meyts I, Baumann U, Kanariou M, Grimbacher B, Hauck F, Graf D, Granado LIG, Prader S, Reisli I, Slatter M, Rodríguez-Gallego C, Arkwright PD, Bethune C, Deripapa E, Sharapova SO, Lehmberg K, Davies EG, Schuetz C, Kindle G, Schubert R
J Clin Immunol 2021 Nov;41(8):1878-1892. Epub 2021 Sep 3 doi: 10.1007/s10875-021-01090-8. PMID: 34477998Free PMC Article
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

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
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
Mücke M, Weier M, Carter C, Copeland J, Degenhardt L, Cuhls H, Radbruch L, Häuser W, Conrad R
J Cachexia Sarcopenia Muscle 2018 Apr;9(2):220-234. Epub 2018 Feb 5 doi: 10.1002/jcsm.12273. PMID: 29400010Free PMC Article
Hernandez AV, Thota P, Pellegrino D, Pasupuleti V, Benites-Zapata VA, Deshpande A, Penalva de Oliveira AC, Vidal JE
HIV Med 2017 Feb;18(2):115-124. Epub 2016 Jun 28 doi: 10.1111/hiv.12402. PMID: 27353303

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