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Immunodeficiency 95(IMD95)

MedGen UID:
1802205
Concept ID:
C5676929
Disease or Syndrome
Synonym: IMD95
 
Gene (location): IFIH1 (2q24.2)
 
Monarch Initiative: MONDO:0030692
OMIM®: 619773

Definition

Immunodeficiency-95 (IMD95) is an autosomal recessive disorder characterized predominantly by the onset of recurrent and severe viral respiratory infections in infancy or early childhood. Affected individuals often require hospitalization or respiratory support for these infections, which include human rhinovirus (HRV) and RSV. Immunologic workup is usually normal, although some mild abnormalities may be observed. The disorder results from a loss of ability of the innate immune system to sense viral genetic information, which causes a lack of interferon (IFN) production, poor response to viral and immunologic stimulation, and failure to control viral replication (summary by Lamborn et al., 2017, Asgari et al., 2017, Cananzi et al., 2021). [from OMIM]

Clinical features

From HPO
Respiratory distress
MedGen UID:
96907
Concept ID:
C0476273
Sign or Symptom
Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.
Respiratory failure
MedGen UID:
257837
Concept ID:
C1145670
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Recurrent viral pneumonia
MedGen UID:
1734666
Concept ID:
C5421686
Finding
Increased susceptibility to viral pneumonia, as manifested by recurrent episodes of viral pneumonias.
Ground-glass opacification
MedGen UID:
1779663
Concept ID:
C5539411
Finding
On chest radiographs, ground-glass opacity appears as an area of hazy increased lung opacity, usually extensive, within which margins of pulmonary vessels may be indistinct. On CT scans, it appears as hazy increased opacity of lung, with preservation of bronchial and vascular margins. It is caused by partial filling of airspaces, interstitial thickening (due to fluid, cells, and/or fibrosis), partial collapse of alveoli, increased capillary blood volume, or a combination of these, the common factor being the partial displacement of air. Ground-glass opacity is less opaque than consolidation, in which bronchovascular margins are obscured.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Decreased circulating IgG3 concentration
MedGen UID:
1686383
Concept ID:
C5139155
Finding
A reduction in immunoglobulin levels of the IgG3 subclass in the blood circulation.
Increased circulating IgG3 level
MedGen UID:
1687845
Concept ID:
C5139254
Finding
An abnormally increased concentration of the IgG3 subtype in the blood circulation.
Recurrent viral upper respiratory tract infections
MedGen UID:
1739717
Concept ID:
C5421654
Finding
An increased susceptibility to viral upper respiratory tract infections as manifested by a history of recurrent viral upper respiratory tract infections (otitis, sinusitis, pharyngitis, tonsillitis).
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.

Professional guidelines

PubMed

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Recent clinical studies

Etiology

Ma H, Zhu F, Zhai H, Ma Y, Liu Y, Wang S, Xu Y
AIDS Care 2023 Feb;35(2):153-164. Epub 2022 May 31 doi: 10.1080/09540121.2022.2080802. PMID: 35642250
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Scand J Immunol 2022 Jun;95(6):e13163. Epub 2022 Mar 23 doi: 10.1111/sji.13163. PMID: 35303369
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
Goudouris ES, Segundo GRS, Poli C
J Pediatr (Rio J) 2019 Mar-Apr;95 Suppl 1:49-58. Epub 2018 Dec 26 doi: 10.1016/j.jped.2018.11.006. PMID: 30593791
Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, Kleoudis C, Groark J, Bass D, Fox NL, Roth D, Gordon D
Arthritis Rheumatol 2017 May;69(5):1016-1027. Epub 2017 Apr 7 doi: 10.1002/art.40049. PMID: 28118533Free PMC Article

Diagnosis

Thakar MS, Logan BR, Puck JM, Dunn EA, Buckley RH, Cowan MJ, O'Reilly RJ, Kapoor N, Satter LF, Pai SY, Heimall J, Chandra S, Ebens CL, Chellapandian D, Williams O, Burroughs LM, Saldana BD, Rayes A, Madden LM, Chandrakasan S, Bednarski JJ 2nd, DeSantes KB, Cuvelier GDE, Teira P, Gillio AP, Eissa H, Knutsen AP, Goldman FD, Aquino VM, Shereck EB, Moore TB, Caywood EH, Lugt MTV, Rozmus J, Broglie L, Yu LC, Shah AJ, Andolina JR, Liu X, Parrott RE, Dara J, Prockop S, Martinez CA, Kapadia M, Jyonouchi SC, Sullivan KE, Bleesing JJ, Chaudhury S, Petrovic A, Keller MD, Quigg TC, Parikh S, Shenoy S, Seroogy C, Rubin T, Decaluwe H, Routes JM, Torgerson TR, Leiding JW, Pulsipher MA, Kohn DB, Griffith LM, Haddad E, Dvorak CC, Notarangelo LD
Lancet 2023 Jul 8;402(10396):129-140. Epub 2023 Jun 20 doi: 10.1016/S0140-6736(23)00731-6. PMID: 37352885Free PMC Article
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
Ayano G, Demelash S, Abraha M, Tsegay L
AIDS Res Ther 2021 Apr 27;18(1):23. doi: 10.1186/s12981-021-00351-1. PMID: 33906698Free PMC Article
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Therapy

Huang Y, Wang CY
Biometrics 2018 Mar;74(1):118-126. Epub 2017 Jul 6 doi: 10.1111/biom.12741. PMID: 28682458Free PMC Article
van Luenen S, Garnefski N, Spinhoven P, Spaan P, Dusseldorp E, Kraaij V
AIDS Behav 2018 Jan;22(1):9-42. doi: 10.1007/s10461-017-1757-y. PMID: 28361453Free PMC Article
Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, Kleoudis C, Groark J, Bass D, Fox NL, Roth D, Gordon D
Arthritis Rheumatol 2017 May;69(5):1016-1027. Epub 2017 Apr 7 doi: 10.1002/art.40049. PMID: 28118533Free PMC Article
Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Cottle L, Zhang XC, Makhema J, Mills LA, Panchia R, Faesen S, Eron J, Gallant J, Havlir D, Swindells S, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano DD, Essex M, Hudelson SE, Redd AD, Fleming TR; HPTN 052 Study Team
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Prognosis

Vallée TC, Glasmacher JS, Buchner H, Arkwright PD, Behrends U, Bondarenko A, Browning MJ, Buchbinder D, Cattoni A, Chernyshova L, Ciznar P, Cole T, Czogała W, Dueckers G, Edgar JDM, Erbey F, Fasth A, Ferrua F, Formankova R, Gambineri E, Gennery AR, Goldman FD, Gonzalez-Granado LI, Heilmann C, Heiskanen-Kosma T, Juntti H, Kainulainen L, Kanegane H, Karaca NE, Kilic SS, Klein C, Kołtan S, Kondratenko I, Meyts I, Nasrullayeva GM, Notarangelo LD, Pasic S, Pellier I, Pignata C, Misbah S, Schulz A, Segundo GR, Shcherbina A, Slatter M, Sokolic R, Soler-Palacin P, Stepensky P, van Montfrans JM, Ryhänen S, Wolska-Kuśnierz B, Ziegler JB, Zhao X, Aiuti A, Ochs HD, Albert MH
Blood 2024 Jun 13;143(24):2504-2516. doi: 10.1182/blood.2023021411. PMID: 38579284
Ibrahim Khalil A, Franceschi S, de Martel C, Bray F, Clifford GM
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Jolles S, Smith BD, Vinh DC, Mallick R, Espinoza G, DeKoven M, Divino V
Leuk Lymphoma 2022 Jan;63(1):64-73. Epub 2021 Oct 26 doi: 10.1080/10428194.2021.1992761. PMID: 34702119
GBD 2017 HIV collaborators
Lancet HIV 2019 Dec;6(12):e831-e859. Epub 2019 Aug 19 doi: 10.1016/S2352-3018(19)30196-1. PMID: 31439534Free PMC Article
van Os NJH, Jansen AFM, van Deuren M, Haraldsson A, van Driel NTM, Etzioni A, van der Flier M, Haaxma CA, Morio T, Rawat A, Schoenaker MHD, Soresina A, Taylor AMR, van de Warrenburg BPC, Weemaes CMR, Roeleveld N, Willemsen MAAP
Clin Immunol 2017 May;178:45-55. Epub 2017 Jan 24 doi: 10.1016/j.clim.2017.01.009. PMID: 28126470

Clinical prediction guides

Badolato R, Alsina L, Azar A, Bertrand Y, Bolyard AA, Dale D, Deyà-Martínez À, Dickerson KE, Ezra N, Hasle H, Kang HJ, Kiani-Alikhan S, Kuijpers TW, Kulagin A, Langguth D, Levin C, Neth O, Olbrich P, Peake J, Rodina Y, Rutten CE, Shcherbina A, Tarrant TK, Vossen MG, Wysocki CA, Belschner A, Bridger GJ, Chen K, Dubuc S, Hu Y, Jiang H, Li S, MacLeod R, Stewart M, Taveras AG, Yan T, Donadieu J
Blood 2024 Jul 4;144(1):35-45. doi: 10.1182/blood.2023022658. PMID: 38643510Free PMC Article
Nardelli GG, Gaudenci EM, Silveira RED, Garcia LAA, Malaquias BSS, Santos ÁDS
Rev Soc Bras Med Trop 2019 May 16;52:e20180355. doi: 10.1590/0037-86820355-2018. PMID: 31141049
Leal JA, Fausto MA, Carneiro M, Tubinambás U
Rev Soc Bras Med Trop 2018 Mar-Apr;51(2):203-206. doi: 10.1590/0037-8682-0093-2017. PMID: 29768554
Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, Kleoudis C, Groark J, Bass D, Fox NL, Roth D, Gordon D
Arthritis Rheumatol 2017 May;69(5):1016-1027. Epub 2017 Apr 7 doi: 10.1002/art.40049. PMID: 28118533Free PMC Article
Hadizadeh H, Salehi M, Khoramnejad S, Vosoughi K, Rezaei N
Pediatr Allergy Immunol 2017 May;28(3):280-287. Epub 2017 Feb 22 doi: 10.1111/pai.12685. PMID: 27893166

Recent systematic reviews

Senécal J, Smyth E, Del Corpo O, Hsu JM, Amar-Zifkin A, Bergeron A, Cheng MP, Butler-Laporte G, McDonald EG, Lee TC
Clin Microbiol Infect 2022 Jan;28(1):23-30. Epub 2021 Aug 28 doi: 10.1016/j.cmi.2021.08.017. PMID: 34464734
Ayano G, Demelash S, Abraha M, Tsegay L
AIDS Res Ther 2021 Apr 27;18(1):23. doi: 10.1186/s12981-021-00351-1. PMID: 33906698Free PMC Article
Peebles K, Velloza J, Balkus JE, McClelland RS, Barnabas RV
Sex Transm Dis 2019 May;46(5):304-311. doi: 10.1097/OLQ.0000000000000972. PMID: 30624309
Heidary M, Nasiri MJ, Mirsaeidi M, Jazi FM, Khoshnood S, Drancourt M, Darban-Sarokhalil D
J Cell Physiol 2019 Jul;234(7):9994-10001. Epub 2018 Dec 12 doi: 10.1002/jcp.27859. PMID: 30548598
Pormohammad A, Nasiri MJ, Riahi SM, Fallah F
Trop Med Int Health 2018 Jun;23(6):589-595. Epub 2018 May 21 doi: 10.1111/tmi.13059. PMID: 29660820

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