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Immunodeficiency 76(IMD76)

MedGen UID:
1781281
Concept ID:
C5543004
Disease or Syndrome
Synonyms: IMD76; IMMUNODEFICIENCY 76
 
Gene (location): FCHO1 (19p13.11)
 
Monarch Initiative: MONDO:0030898
OMIM®: 619164

Definition

Immunodeficiency-76 (IMD76) is an autosomal recessive primary immunologic disorder characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Laboratory studies show T-cell lymphopenia and may show variable B-cell or immunoglobulin abnormalities. More variable features found in some patients include lymphoma and neurologic features. Although bone marrow transplantation may be curative, many patients die in childhood (summary by Lyszkiewicz et al., 2020). [from OMIM]

Clinical features

From HPO
B-cell lymphoma
MedGen UID:
86953
Concept ID:
C0079731
Neoplastic Process
A type of lymphoma that originates in B-cells.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Colitis
MedGen UID:
40385
Concept ID:
C0009319
Disease or Syndrome
Ulcerative colitis is a chronic disorder that affects the digestive system. This condition is characterized by abnormal inflammation of the inner surface (epithelium) of the rectum and colon. The rectum and colon make up most of the length of the large intestine. The inflammation usually causes open sores (ulcers) to develop in the large intestine. Ulcerative colitis usually appears between the age of 15 and 30, although it can develop at any age. The inflammation tends to flare up multiple times throughout a person's life, which causes recurring signs and symptoms.\n\nThe most common symptoms of ulcerative colitis are cramping abdominal pain and frequent diarrhea, often with blood, pus, or mucus in the stool. Other signs and symptoms include nausea, loss of appetite, bowel urgency, fatigue, and fevers. Chronic bleeding from the inflamed and ulcerated intestinal tissue can cause a shortage of red blood cells (anemia) in some affected individuals. People with this disorder have difficulty absorbing enough fluids and nutrients from their diet and often experience weight loss. Affected children usually grow more slowly than normal. Less commonly, ulcerative colitis causes problems with the skin, joints, eyes, kidneys, or liver, which are most likely due to abnormal inflammation.\n\nToxic megacolon is a rare complication of ulcerative colitis that can be life-threatening. Toxic megacolon involves a widening (dilation) of the colon and an overwhelming inflammatory response. Ulcerative colitis also increases the risk of developing colon cancer, especially in people whose entire colon is inflamed and in those who have had ulcerative colitis for 8 years or more.\n\nUlcerative colitis is one common form of inflammatory bowel disease (IBD). Another type of IBD, Crohn's disease, also causes chronic inflammation of the intestines. Unlike ulcerative colitis, which affects only the inner surface of the large intestine, Crohn's disease can cause inflammation in any part of the digestive system, and the inflammation extends deeper into the intestinal tissue.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Recurrent bronchiolitis
MedGen UID:
863573
Concept ID:
C4015136
Finding
An increased susceptibility to bronchiolitis as manifested by a history of recurrent bronchiolitis.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargment (swelling) of a lymph node.
B lymphocytopenia
MedGen UID:
340780
Concept ID:
C1855067
Finding
An abnormal decrease from the normal count of B cells.
T lymphocytopenia
MedGen UID:
419385
Concept ID:
C2931322
Finding
An abnormally low count of T cells.

Professional guidelines

PubMed

Pan H, Wang G, Guan E, Song L, Song A, Liu X, Yi Z, Sun LR
BMC Pediatr 2020 Jun 9;20(1):288. doi: 10.1186/s12887-020-02178-7. PMID: 32517812Free PMC Article

Recent clinical studies

Etiology

Fan L, Li C, Zhao H
Biomed Res Int 2020;2020:3132589. Epub 2020 Jan 28 doi: 10.1155/2020/3132589. PMID: 32090076Free PMC Article
Kluger N
Curr Probl Dermatol 2015;48:76-87. Epub 2015 Mar 26 doi: 10.1159/000369189. PMID: 25833628
Spinner MA, Sanchez LA, Hsu AP, Shaw PA, Zerbe CS, Calvo KR, Arthur DC, Gu W, Gould CM, Brewer CC, Cowen EW, Freeman AF, Olivier KN, Uzel G, Zelazny AM, Daub JR, Spalding CD, Claypool RJ, Giri NK, Alter BP, Mace EM, Orange JS, Cuellar-Rodriguez J, Hickstein DD, Holland SM
Blood 2014 Feb 6;123(6):809-21. Epub 2013 Nov 13 doi: 10.1182/blood-2013-07-515528. PMID: 24227816Free PMC Article
Cossu F
Ital J Pediatr 2010 Nov 15;36:76. doi: 10.1186/1824-7288-36-76. PMID: 21078154Free PMC Article
Carswell JW
Br Med Bull 1988 Jan;44(1):183-202. doi: 10.1093/oxfordjournals.bmb.a072240. PMID: 3058246

Diagnosis

Lev A, Asleh M, Levy S, Lee YN, Simon AJ, Stepensky P, Nalbandyan K, Nahum A, Ben-Harosh M, Yablonski D, Broides A, Somech R
J Clin Immunol 2023 Apr;43(3):625-635. Epub 2022 Dec 7 doi: 10.1007/s10875-022-01412-4. PMID: 36474126
Mateu L, Teniente-Serra A, Rocamora G, Marin-Muñiz A, Pàrraga N, Casas I, Reynaga E, Sopena N, Sabria M, Pedro-Botet ML; los miembros del Comité de Inmunodeficiencias Primarias del Hospital Germans Trias i Pujol
Med Clin (Barc) 2021 Mar 26;156(6):270-276. Epub 2020 Aug 28 doi: 10.1016/j.medcli.2020.04.066. PMID: 32868033
Spinner MA, Sanchez LA, Hsu AP, Shaw PA, Zerbe CS, Calvo KR, Arthur DC, Gu W, Gould CM, Brewer CC, Cowen EW, Freeman AF, Olivier KN, Uzel G, Zelazny AM, Daub JR, Spalding CD, Claypool RJ, Giri NK, Alter BP, Mace EM, Orange JS, Cuellar-Rodriguez J, Hickstein DD, Holland SM
Blood 2014 Feb 6;123(6):809-21. Epub 2013 Nov 13 doi: 10.1182/blood-2013-07-515528. PMID: 24227816Free PMC Article
Clucas C, Sibley E, Harding R, Liu L, Catalan J, Sherr L
Psychol Health Med 2011 Oct;16(5):528-47. Epub 2011 Jul 21 doi: 10.1080/13548506.2011.579989. PMID: 21777090
Cossu F
Ital J Pediatr 2010 Nov 15;36:76. doi: 10.1186/1824-7288-36-76. PMID: 21078154Free PMC Article

Therapy

Magnani A, Semeraro M, Adam F, Booth C, Dupré L, Morris EC, Gabrion A, Roudaut C, Borgel D, Toubert A, Clave E, Abdo C, Gorochov G, Petermann R, Guiot M, Miyara M, Moshous D, Magrin E, Denis A, Suarez F, Lagresle C, Roche AM, Everett J, Trinquand A, Guisset M, Bayford JX, Hacein-Bey-Abina S, Kauskot A, Elfeky R, Rivat C, Abbas S, Gaspar HB, Macintyre E, Picard C, Bushman FD, Galy A, Fischer A, Six E, Thrasher AJ, Cavazzana M
Nat Med 2022 Jan;28(1):71-80. Epub 2022 Jan 24 doi: 10.1038/s41591-021-01641-x. PMID: 35075289Free PMC Article
Robinson HL
Clin Pharmacol Ther 2018 Dec;104(6):1062-1073. Epub 2018 Oct 9 doi: 10.1002/cpt.1208. PMID: 30099743Free 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
Keating GM
BioDrugs 2008;22(3):177-88. doi: 10.2165/00063030-200822030-00004. PMID: 18481900

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
Wu MY, Gong HZ, Hu KR, Zheng HY, Wan X, Li J
Sex Transm Infect 2021 Nov;97(7):525-533. Epub 2020 Nov 20 doi: 10.1136/sextrans-2020-054706. PMID: 33219164Free PMC Article
Chiesa R, Wang J, Blok HJ, Hazelaar S, Neven B, Moshous D, Schulz A, Hoenig M, Hauck F, Al Seraihy A, Gozdzik J, Ljungman P, Lindemans CA, Fernandes JF, Kalwak K, Strahm B, Schanz U, Sedlacek P, Sykora KW, Aksoylar S, Locatelli F, Stepensky P, Wynn R, Lum SH, Zecca M, Porta F, Taskinen M, Gibson B, Matthes S, Karakukcu M, Hauri-Hohl M, Veys P, Gennery AR, Lucchini G, Felber M, Albert MH, Balashov D, Lankester A, Güngör T, Slatter MA
Blood 2020 Sep 3;136(10):1201-1211. doi: 10.1182/blood.2020005590. PMID: 32614953
Murray CJ, Ortblad KF, Guinovart C, Lim SS, Wolock TM, Roberts DA, Dansereau EA, Graetz N, Barber RM, Brown JC, Wang H, Duber HC, Naghavi M, Dicker D, Dandona L, Salomon JA, Heuton KR, Foreman K, Phillips DE, Fleming TD, Flaxman AD, Phillips BK, Johnson EK, Coggeshall MS, Abd-Allah F, Abera SF, Abraham JP, Abubakar I, Abu-Raddad LJ, Abu-Rmeileh NM, Achoki T, Adeyemo AO, Adou AK, Adsuar JC, Agardh EE, Akena D, Al Kahbouri MJ, Alasfoor D, Albittar MI, Alcalá-Cerra G, Alegretti MA, Alemu ZA, Alfonso-Cristancho R, Alhabib S, Ali R, Alla F, Allen PJ, Alsharif U, Alvarez E, Alvis-Guzman N, Amankwaa AA, Amare AT, Amini H, Ammar W, Anderson BO, Antonio CA, Anwari P, Arnlöv J, Arsenijevic VS, Artaman A, Asghar RJ, Assadi R, Atkins LS, Badawi A, Balakrishnan K, Banerjee A, Basu S, Beardsley J, Bekele T, Bell ML, Bernabe E, Beyene TJ, Bhala N, Bhalla A, Bhutta ZA, Abdulhak AB, Binagwaho A, Blore JD, Basara BB, Bose D, Brainin M, Breitborde N, Castañeda-Orjuela CA, Catalá-López F, Chadha VK, Chang JC, Chiang PP, Chuang TW, Colomar M, Cooper LT, Cooper C, Courville KJ, Cowie BC, Criqui MH, Dandona R, Dayama A, De Leo D, Degenhardt L, Del Pozo-Cruz B, Deribe K, Des Jarlais DC, Dessalegn M, Dharmaratne SD, Dilmen U, Ding EL, Driscoll TR, Durrani AM, Ellenbogen RG, Ermakov SP, Esteghamati A, Faraon EJ, Farzadfar F, Fereshtehnejad SM, Fijabi DO, Forouzanfar MH, Fra Paleo U, Gaffikin L, Gamkrelidze A, Gankpé FG, Geleijnse JM, Gessner BD, Gibney KB, Ginawi IA, Glaser EL, Gona P, Goto A, Gouda HN, Gugnani HC, Gupta R, Gupta R, Hafezi-Nejad N, Hamadeh RR, Hammami M, Hankey GJ, Harb HL, Haro JM, Havmoeller R, Hay SI, Hedayati MT, Pi IB, Hoek HW, Hornberger JC, Hosgood HD, Hotez PJ, Hoy DG, Huang JJ, Iburg KM, Idrisov BT, Innos K, Jacobsen KH, Jeemon P, Jensen PN, Jha V, Jiang G, Jonas JB, Juel K, Kan H, Kankindi I, Karam NE, Karch A, Karema CK, Kaul A, Kawakami N, Kazi DS, Kemp AH, Kengne AP, Keren A, Kereselidze M, Khader YS, Khalifa SE, Khan EA, Khang YH, Khonelidze I, Kinfu Y, Kinge JM, Knibbs L, Kokubo Y, Kosen S, Defo BK, Kulkarni VS, Kulkarni C, Kumar K, Kumar RB, Kumar GA, Kwan GF, Lai T, Balaji AL, Lam H, Lan Q, Lansingh VC, Larson HJ, Larsson A, Lee JT, Leigh J, Leinsalu M, Leung R, Li Y, Li Y, De Lima GM, Lin HH, Lipshultz SE, Liu S, Liu Y, Lloyd BK, Lotufo PA, Machado VM, Maclachlan JH, Magis-Rodriguez C, Majdan M, Mapoma CC, Marcenes W, Marzan MB, Masci JR, Mashal MT, Mason-Jones AJ, Mayosi BM, Mazorodze TT, Mckay AC, Meaney PA, Mehndiratta MM, Mejia-Rodriguez F, Melaku YA, Memish ZA, Mendoza W, Miller TR, Mills EJ, Mohammad KA, Mokdad AH, Mola GL, Monasta L, Montico M, Moore AR, Mori R, Moturi WN, Mukaigawara M, Murthy KS, Naheed A, Naidoo KS, Naldi L, Nangia V, Narayan KM, Nash D, Nejjari C, Nelson RG, Neupane SP, Newton CR, Ng M, Nisar MI, Nolte S, Norheim OF, Nowaseb V, Nyakarahuka L, Oh IH, Ohkubo T, Olusanya BO, Omer SB, Opio JN, Orisakwe OE, Pandian JD, Papachristou C, Caicedo AJ, Patten SB, Paul VK, Pavlin BI, Pearce N, Pereira DM, Pervaiz A, Pesudovs K, Petzold M, Pourmalek F, Qato D, Quezada AD, Quistberg DA, Rafay A, Rahimi K, Rahimi-Movaghar V, Ur Rahman S, Raju M, Rana SM, Razavi H, Reilly RQ, Remuzzi G, Richardus JH, Ronfani L, Roy N, Sabin N, Saeedi MY, Sahraian MA, Samonte GM, Sawhney M, Schneider IJ, Schwebel DC, Seedat S, Sepanlou SG, Servan-Mori EE, Sheikhbahaei S, Shibuya K, Shin HH, Shiue I, Shivakoti R, Sigfusdottir ID, Silberberg DH, Silva AP, Simard EP, Singh JA, Skirbekk V, Sliwa K, Soneji S, Soshnikov SS, Sreeramareddy CT, Stathopoulou VK, Stroumpoulis K, Swaminathan S, Sykes BL, Tabb KM, Talongwa RT, Tenkorang EY, Terkawi AS, Thomson AJ, Thorne-Lyman AL, Towbin JA, Traebert J, Tran BX, Dimbuene ZT, Tsilimbaris M, Uchendu US, Ukwaja KN, Uzun SB, Vallely AJ, Vasankari TJ, Venketasubramanian N, Violante FS, Vlassov VV, Vollset SE, Waller S, Wallin MT, Wang L, Wang X, Wang Y, Weichenthal S, Weiderpass E, Weintraub RG, Westerman R, White RA, Wilkinson JD, Williams TN, Woldeyohannes SM, Wong JQ, Xu G, Yang YC, Yano Y, Yentur GK, Yip P, Yonemoto N, Yoon SJ, Younis M, Yu C, Jin KY, El Sayed Zaki M, Zhao Y, Zheng Y, Zhou M, Zhu J, Zou XN, Lopez AD, Vos T
Lancet 2014 Sep 13;384(9947):1005-70. Epub 2014 Jul 22 doi: 10.1016/S0140-6736(14)60844-8. PMID: 25059949Free PMC Article
Spinner MA, Sanchez LA, Hsu AP, Shaw PA, Zerbe CS, Calvo KR, Arthur DC, Gu W, Gould CM, Brewer CC, Cowen EW, Freeman AF, Olivier KN, Uzel G, Zelazny AM, Daub JR, Spalding CD, Claypool RJ, Giri NK, Alter BP, Mace EM, Orange JS, Cuellar-Rodriguez J, Hickstein DD, Holland SM
Blood 2014 Feb 6;123(6):809-21. Epub 2013 Nov 13 doi: 10.1182/blood-2013-07-515528. PMID: 24227816Free PMC Article

Clinical prediction guides

Arrieta-Martínez JA, Estrada-Acevedo JI, Gómez CA, Madrigal-Cadavid J, Serna JA, Giraldo PA, Quirós-Gómez Ó
Farm Hosp 2022 Nov 24;46(6):319-326. PMID: 36520570
Brinker MR, Loftis CM, Khoriaty JD, Dunn WR
J Shoulder Elbow Surg 2022 Dec;31(12):2578-2585. Epub 2022 Jun 16 doi: 10.1016/j.jse.2022.05.012. PMID: 35718254
Shen Q, Sheng L, Zhang J, Ye J, Zhou J
Infection 2022 Feb;50(1):169-178. Epub 2021 Aug 5 doi: 10.1007/s15010-021-01679-6. PMID: 34351597Free PMC Article
Tordoff DM, Barbee LA, Khosropour CM, Hughes JP, Golden MR
J Acquir Immune Defic Syndr 2020 Nov 1;85(3):263-271. doi: 10.1097/QAI.0000000000002438. PMID: 32658131
Banting J, Meriano T
J Spec Oper Med 2017 Spring;17(1):76. doi: 10.55460/386W-D689. PMID: 28285484

Recent systematic reviews

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
Sultana ZZ, Hoque FU, Beyene J, Akhlak-Ul-Islam M, Khan MHR, Ahmed S, Hawlader DH, Hossain A
BMC Infect Dis 2021 Jan 11;21(1):51. doi: 10.1186/s12879-020-05749-2. PMID: 33430786Free PMC Article
Degenhardt L, Peacock A, Colledge S, Leung J, Grebely J, Vickerman P, Stone J, Cunningham EB, Trickey A, Dumchev K, Lynskey M, Griffiths P, Mattick RP, Hickman M, Larney S
Lancet Glob Health 2017 Dec;5(12):e1192-e1207. Epub 2017 Oct 23 doi: 10.1016/S2214-109X(17)30375-3. PMID: 29074409Free 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

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