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Immunodeficiency 96(IMD96)

MedGen UID:
1810465
Concept ID:
C5676930
Disease or Syndrome
Synonym: IMD96
 
Gene (location): LIG1 (19q13.33)
 
Monarch Initiative: MONDO:0030693
OMIM®: 619774

Definition

Immunodeficiency-96 (IMD96) is an autosomal recessive disorder characterized by onset of recurrent, usually viral, respiratory infections in infancy or early childhood. Other infections, including gastrointestinal and urinary tract infections, may also occur. Laboratory studies show hypogammaglobulinemia, lymphopenia with increased gamma/delta T cells, and erythrocyte macrocytosis. The disorder results from defective cellular DNA repair (summary by Maffucci et al., 2018). [from OMIM]

Clinical features

From HPO
Multicystic kidney dysplasia
MedGen UID:
811388
Concept ID:
C3714581
Disease or Syndrome
Multicystic dysplasia of the kidney is characterized by multiple cysts of varying size in the kidney and the absence of a normal pelvicaliceal system. The condition is associated with ureteral or ureteropelvic atresia, and the affected kidney is nonfunctional.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Increased mean corpuscular volume
MedGen UID:
81303
Concept ID:
C0302845
Finding
Larger than normal size of erythrocytes.
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.
Eczema
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis. The term eczema is broadly applied to a range of persistent skin conditions and can be related to a number of underlying conditions. Manifestations of eczema can include dryness and recurring skin rashes with redness, skin edema, itching and dryness, crusting, flaking, blistering, cracking, oozing, or bleeding.
Decreased circulating IgA level
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 infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
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.
Decreased circulating IgG level
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Increased proportion of gamma-delta T cells
MedGen UID:
1712401
Concept ID:
C5398019
Finding
Increased proportion of gamma-delta T cells relative to the total number of T cells.
Conjunctival telangiectasia
MedGen UID:
66780
Concept ID:
C0239105
Disease or Syndrome
The presence of small (ca. 0.5-1.0 mm) dilated blood vessels near the surface of the mucous membranes of the conjunctiva.

Professional guidelines

PubMed

Bares SH, Scarsi KK
Curr Opin HIV AIDS 2022 Jan 1;17(1):22-31. doi: 10.1097/COH.0000000000000708. PMID: 34871188Free PMC Article
Stockdale AJ, Khoo S
Curr Opin HIV AIDS 2022 Jan 1;17(1):4-14. doi: 10.1097/COH.0000000000000709. PMID: 34740228
Hill AM, Moecklinghoff C, DeMasi R
Int J STD AIDS 2015 Mar;26(4):268-78. Epub 2014 May 29 doi: 10.1177/0956462414536885. PMID: 24874537

Recent clinical studies

Etiology

Sun C, Li J, Liu X, Zhang Z, Qiu T, Hu H, Wang Y, Fu G
AIDS Res Ther 2021 Dec 11;18(1):96. doi: 10.1186/s12981-021-00415-2. PMID: 34895254Free PMC Article
Wang L, Zhang Z, Xu R, Wang X, Shu Z, Chen X, Wang S, Liu J, Li Y, Wang L, Zhang M, Yang W, Wang Y, Huang H, Tu B, Liang Z, Li L, Li J, Hou Y, Shi M, Wang FS
Signal Transduct Target Ther 2021 Jun 9;6(1):217. doi: 10.1038/s41392-021-00607-2. PMID: 34103473Free PMC Article
Temfack E, Rim JJB, Spijker R, Loyse A, Chiller T, Pappas PG, Perfect J, Sorell TC, Harrison TS, Cohen JF, Lortholary O
Clin Infect Dis 2021 Apr 8;72(7):1268-1278. doi: 10.1093/cid/ciaa1243. PMID: 32829406Free PMC Article
Chu C, Pollock LC, Selwyn PA
Am Fam Physician 2017 Aug 1;96(3):161-169. PMID: 28762691
Coates TJ, Collins C
Sci Am 1998 Jul;279(1):96-7. doi: 10.1038/scientificamerican0798-96. PMID: 9648304

Diagnosis

Sun C, Li J, Liu X, Zhang Z, Qiu T, Hu H, Wang Y, Fu G
AIDS Res Ther 2021 Dec 11;18(1):96. doi: 10.1186/s12981-021-00415-2. PMID: 34895254Free PMC Article
Temfack E, Rim JJB, Spijker R, Loyse A, Chiller T, Pappas PG, Perfect J, Sorell TC, Harrison TS, Cohen JF, Lortholary O
Clin Infect Dis 2021 Apr 8;72(7):1268-1278. doi: 10.1093/cid/ciaa1243. PMID: 32829406Free PMC Article
Nduaguba SO, Ford KH, Wilson JP, Lawson KA
AIDS Care 2021 Mar;33(3):285-289. Epub 2019 Dec 15 doi: 10.1080/09540121.2019.1703890. PMID: 31838894
Hartono S, Ippoliti MR, Mastroianni M, Torres R, Rider NL
Clin Rev Allergy Immunol 2019 Oct;57(2):145-165. doi: 10.1007/s12016-018-8689-9. PMID: 29754192
Valizadeh A
Artif Cells Nanomed Biotechnol 2016 Sep;44(6):1383-90. Epub 2015 Jun 23 doi: 10.3109/21691401.2015.1052469. PMID: 26099718

Therapy

Bares SH, Scarsi KK
Curr Opin HIV AIDS 2022 Jan 1;17(1):22-31. doi: 10.1097/COH.0000000000000708. PMID: 34871188Free PMC Article
Temfack E, Rim JJB, Spijker R, Loyse A, Chiller T, Pappas PG, Perfect J, Sorell TC, Harrison TS, Cohen JF, Lortholary O
Clin Infect Dis 2021 Apr 8;72(7):1268-1278. doi: 10.1093/cid/ciaa1243. PMID: 32829406Free PMC Article
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
Mason-Jones AJ, Sinclair D, Mathews C, Kagee A, Hillman A, Lombard C
Cochrane Database Syst Rev 2016 Nov 8;11(11):CD006417. doi: 10.1002/14651858.CD006417.pub3. PMID: 27824221Free 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
N Engl J Med 2016 Sep 1;375(9):830-9. Epub 2016 Jul 18 doi: 10.1056/NEJMoa1600693. PMID: 27424812Free PMC Article

Prognosis

Wang L, Zhang Z, Xu R, Wang X, Shu Z, Chen X, Wang S, Liu J, Li Y, Wang L, Zhang M, Yang W, Wang Y, Huang H, Tu B, Liang Z, Li L, Li J, Hou Y, Shi M, Wang FS
Signal Transduct Target Ther 2021 Jun 9;6(1):217. doi: 10.1038/s41392-021-00607-2. PMID: 34103473Free PMC Article
Cohen MS, Gamble T, McCauley M
Annu Rev Med 2020 Jan 27;71:347-360. Epub 2019 Oct 25 doi: 10.1146/annurev-med-110918-034551. PMID: 31652410
Chen J, Zhang R, Shen Y, Liu L, Qi T, Wang Z, Song W, Tang Y, Lu H
Am J Trop Med Hyg 2017 Jun;96(6):1350-1354. doi: 10.4269/ajtmh.16-0521. PMID: 28719279Free 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
N Engl J Med 2016 Sep 1;375(9):830-9. Epub 2016 Jul 18 doi: 10.1056/NEJMoa1600693. PMID: 27424812Free PMC Article
Cohen MS, Smith MK, Muessig KE, Hallett TB, Powers KA, Kashuba AD
Lancet 2013 Nov 2;382(9903):1515-24. Epub 2013 Oct 23 doi: 10.1016/S0140-6736(13)61998-4. PMID: 24152938Free PMC Article

Clinical prediction guides

Koethe JR, Moser C, Brown TT, Stein JH, Kelesidis T, Dube M, Currier J, McComsey GA
Clin Infect Dis 2022 Mar 9;74(5):857-864. doi: 10.1093/cid/ciab542. PMID: 34117756Free PMC Article
Wang L, Zhang Z, Xu R, Wang X, Shu Z, Chen X, Wang S, Liu J, Li Y, Wang L, Zhang M, Yang W, Wang Y, Huang H, Tu B, Liang Z, Li L, Li J, Hou Y, Shi M, Wang FS
Signal Transduct Target Ther 2021 Jun 9;6(1):217. doi: 10.1038/s41392-021-00607-2. PMID: 34103473Free PMC Article
Deng L, Zhang X, Gao Y, Turner D, Qian F, Lu H, Vermund SH, Zhang Y, Qian HZ
Ageing Res Rev 2021 Jul;68:101310. Epub 2021 Feb 26 doi: 10.1016/j.arr.2021.101310. PMID: 33640473
Benhsaien I, Ailal F, El Bakkouri J, Jeddane L, Ouair H, Admou B, Bouskraoui M, Hbibi M, Hida M, Amenzoui N, Jouhadi Z, El Hafidi N, Rada N, Benajiba N, Abilkassem R, Badou A, Bousfiha AA
J Clin Immunol 2021 Apr;41(3):631-638. Epub 2021 Jan 7 doi: 10.1007/s10875-020-00960-x. PMID: 33411152
Anglemyer A, Rutherford GW, Horvath T, Baggaley RC, Egger M, Siegfried N
Cochrane Database Syst Rev 2013 Apr 30;4(4):CD009153. doi: 10.1002/14651858.CD009153.pub3. PMID: 23633367Free PMC Article

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
Deng L, Zhang X, Gao Y, Turner D, Qian F, Lu H, Vermund SH, Zhang Y, Qian HZ
Ageing Res Rev 2021 Jul;68:101310. Epub 2021 Feb 26 doi: 10.1016/j.arr.2021.101310. PMID: 33640473
Temfack E, Rim JJB, Spijker R, Loyse A, Chiller T, Pappas PG, Perfect J, Sorell TC, Harrison TS, Cohen JF, Lortholary O
Clin Infect Dis 2021 Apr 8;72(7):1268-1278. doi: 10.1093/cid/ciaa1243. PMID: 32829406Free PMC Article
Del Corpo O, Butler-Laporte G, Sheppard DC, Cheng MP, McDonald EG, Lee TC
Clin Microbiol Infect 2020 Sep;26(9):1137-1143. Epub 2020 May 30 doi: 10.1016/j.cmi.2020.05.024. PMID: 32479781
Kanters S, Vitoria M, Doherty M, Socias ME, Ford N, Forrest JI, Popoff E, Bansback N, Nsanzimana S, Thorlund K, Mills EJ
Lancet HIV 2016 Nov;3(11):e510-e520. Epub 2016 Sep 6 doi: 10.1016/S2352-3018(16)30091-1. PMID: 27658869

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