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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
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by 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.
Eczematoid dermatitis
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
Decreased circulating IgA concentration
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 concentration
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

Li C, Sun JP, Wang N, Yan P, Wang R, Su B, Zhang T, Wu H, Chen H, Li Z, Huang XJ
AIDS Res Hum Retroviruses 2024 Feb;40(2):101-109. Epub 2023 May 30 doi: 10.1089/AID.2022.0089. PMID: 37051683
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
Bland RM
Arch Dis Child 2011 Oct;96(10):911-5. Epub 2011 May 11 doi: 10.1136/adc.2010.193789. PMID: 21562058

Recent clinical studies

Etiology

Yang T, Xie Z, Xu Z, Tu B, Lu H, Huang H, Huang L, Zhang C, Gao L, Jin L, Ma P, Zou J, Liu L, Zhen C, Zhou C, Meng S, Li YY, Song JW, Yang S, Ai HS, Jiao Y, Shi M, Xu R, Wang FS
Emerg Microbes Infect 2024 Dec;13(1):2364744. Epub 2024 Jun 27 doi: 10.1080/22221751.2024.2364744. PMID: 38935839Free 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
Kretschmer S, Lee-Kirsch MA
Curr Opin Immunol 2017 Dec;49:96-102. Epub 2017 Nov 10 doi: 10.1016/j.coi.2017.09.003. PMID: 29128691
Valizadeh A
Artif Cells Nanomed Biotechnol 2016 Sep;44(6):1383-90. Epub 2015 Jun 23 doi: 10.3109/21691401.2015.1052469. PMID: 26099718
Khan S, Pereira J, Darbyshire PJ, Holding S, Doré PC, Sewell WA, Huissoon A
Clin Exp Immunol 2011 Jan;163(1):96-103. Epub 2010 Nov 9 doi: 10.1111/j.1365-2249.2010.04280.x. PMID: 21062271Free PMC Article

Diagnosis

Secher S, Hentzien M, Cuzin L, Jacomet C, Hocqueloux L, Rey D, Menard A, Arvieux C, Raffi F, Bani-Sadr F
AIDS Res Hum Retroviruses 2024 Apr;40(4):253-256. Epub 2023 Oct 18 doi: 10.1089/AID.2023.0050. PMID: 37756371
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
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
Khan S, Pereira J, Darbyshire PJ, Holding S, Doré PC, Sewell WA, Huissoon A
Clin Exp Immunol 2011 Jan;163(1):96-103. Epub 2010 Nov 9 doi: 10.1111/j.1365-2249.2010.04280.x. PMID: 21062271Free PMC Article
Serraino D, Franceschi S, Tirelli U, Monfardini S
Ann Oncol 1992 Sep;3(8):595-603. doi: 10.1093/oxfordjournals.annonc.a058283. PMID: 1450040

Therapy

Craig TJ, Reshef A, Li HH, Jacobs JS, Bernstein JA, Farkas H, Yang WH, Stroes ESG, Ohsawa I, Tachdjian R, Manning ME, Lumry WR, Saguer IM, Aygören-Pürsün E, Ritchie B, Sussman GL, Anderson J, Kawahata K, Suzuki Y, Staubach P, Treudler R, Feuersenger H, Glassman F, Jacobs I, Magerl M
Lancet 2023 Apr 1;401(10382):1079-1090. Epub 2023 Feb 28 doi: 10.1016/S0140-6736(23)00350-1. PMID: 36868261
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
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
Cambiano V, O'Connor J, Phillips AN, Rodger A, Lodwick R, Pharris A, Lampe F, Nakagawa F, Smith C, van de Laar MJ
Euro Surveill 2013 Nov 28;18(48):20647. doi: 10.2807/1560-7917.es2013.18.48.20647. PMID: 24308982
Zou W, Berglund L
Prev Cardiol 2007 Spring;10(2):96-103; quiz 104-5. doi: 10.1111/j.1520-037x.2007.03071.x. PMID: 17392622

Prognosis

Li J, Xie DD, Cui HL, Yue C, Wang QY, Luo C, Tian L, Sheng ZF
J Med Virol 2024 Jun;96(6):e29724. doi: 10.1002/jmv.29724. PMID: 38837426
Wan Z, Sun P, Dzakah EE, Huang L, Shuai P, Liu Y
Front Public Health 2022;10:855989. Epub 2022 Jul 29 doi: 10.3389/fpubh.2022.855989. PMID: 35968434Free PMC Article
Glick Y, Dubin I, Schattner A
Postgrad Med J 2020 Nov;96(1141):719. Epub 2020 Jan 5 doi: 10.1136/postgradmedj-2019-137211. PMID: 31907226
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
Longstreth J
Environ Health Perspect 1991 Dec;96:139-44. doi: 10.1289/ehp.9196139. PMID: 1820256Free PMC Article

Clinical prediction guides

Yang T, Xie Z, Xu Z, Tu B, Lu H, Huang H, Huang L, Zhang C, Gao L, Jin L, Ma P, Zou J, Liu L, Zhen C, Zhou C, Meng S, Li YY, Song JW, Yang S, Ai HS, Jiao Y, Shi M, Xu R, Wang FS
Emerg Microbes Infect 2024 Dec;13(1):2364744. Epub 2024 Jun 27 doi: 10.1080/22221751.2024.2364744. PMID: 38935839Free PMC Article
HIV Transmission Elimination AMsterdam (H-TEAM) Initiative
Euro Surveill 2023 Oct;28(40) doi: 10.2807/1560-7917.ES.2023.28.40.2300515. PMID: 37796442Free PMC Article
Patel NC, Torgerson T, Thakar MS, Younger MEM, Sriaroon P, Pozos TC, Buckley RH, Morris D, Vilkama D, Heimall J
J Clin Immunol 2023 Oct;43(7):1557-1565. Epub 2023 Jun 2 doi: 10.1007/s10875-023-01482-y. PMID: 37266769Free PMC Article
Chen W, Zhou X, Ma Q, He L, Chen W, Guo Z, Chen L
PLoS One 2023;18(5):e0283970. Epub 2023 May 25 doi: 10.1371/journal.pone.0283970. PMID: 37228160Free PMC Article
Desta F, Tasew A, Tekalegn Y, Zenbaba D, Sahiledengle B, Assefa T, Negash W, Tahir A, Regasa T, Mamo A, Teferu Z, Solomon D, Gezahegn H, Bekele K, Regassa Z, Atlaw D
BMC Psychiatry 2022 Aug 19;22(1):557. doi: 10.1186/s12888-022-04205-6. PMID: 35986352Free PMC Article

Recent systematic reviews

Wang W, Zhao S, Wu Y, Duan W, Li S, Li Z, Guo C, Wang W, Zhang T, Wu H, Huang X
JMIR Public Health Surveill 2023 Jul 27;9:e46767. doi: 10.2196/46767. PMID: 37498645Free PMC Article
Zhu Y, Liu K, Wang K, Zhu H
Cancer 2023 Jan 15;129(2):283-295. Epub 2022 Nov 21 doi: 10.1002/cncr.34507. PMID: 36408673Free PMC Article
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
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

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