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Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection(IMD44)

MedGen UID:
904009
Concept ID:
C4225260
Disease or Syndrome
Synonym: Immunodeficiency 44
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): STAT2 (12q13.3)
 
Monarch Initiative: MONDO:0014715
OMIM®: 616636
Orphanet: ORPHA431166

Definition

Immunodeficiency-44 (IMD44) is an autosomal recessive primary immunodeficiency characterized by increased susceptibility to viral infections and adverse multisystemic reaction to vaccination in some patients. Affected individuals appear to have defects in mitochondrial fission and fusion (summary by Shahni et al., 2015). [from OMIM]

Clinical features

From HPO
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Elevated CSF neopterin level
MedGen UID:
893002
Concept ID:
C4073152
Finding
Increased concentration of neopterin in the cerebrospinal fluid (CSF).
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
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.
Severe viral infection
MedGen UID:
479058
Concept ID:
C3277428
Finding
An unusually severe viral infection.
Post-vaccination measles
MedGen UID:
1688337
Concept ID:
C5139071
Disease or Syndrome
Infection with the measles virus of the live-attenuated vaccine. This is an extremely rare event and may indicate immunocompromise in some cases.
Abnormal circulating IgG concentration
MedGen UID:
1687987
Concept ID:
C5139422
Finding
An abnormal deviation from normal levels of IgG immunoglobulin in blood.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Increased circulating lactate concentration
MedGen UID:
332209
Concept ID:
C1836440
Finding
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPrimary immunodeficiency with post-measles-mumps-rubella vaccine viral infection

Professional guidelines

PubMed

Drzymalla E, Green RF, Knuth M, Khoury MJ, Dotson WD, Gundlapalli A
Clin Immunol 2022 Oct;243:109097. Epub 2022 Aug 13 doi: 10.1016/j.clim.2022.109097. PMID: 35973637Free PMC Article
Elliman DAC, Gennery AR
Clin Exp Immunol 2021 Sep;205(3):343-345. Epub 2021 Jul 8 doi: 10.1111/cei.13642. PMID: 34235744Free PMC Article
Principi N, Esposito S
Vaccine 2014 Jun 24;32(30):3725-31. Epub 2014 May 14 doi: 10.1016/j.vaccine.2014.05.022. PMID: 24837766

Recent clinical studies

Etiology

Boulware DR, Atukunda M, Kagimu E, Musubire AK, Akampurira A, Tugume L, Ssebambulidde K, Kasibante J, Nsangi L, Mugabi T, Gakuru J, Kimuda S, Kasozi D, Namombwe S, Turyasingura I, Rutakingirwa MK, Mpoza E, Kigozi E, Muzoora C, Ellis J, Skipper CP, Matkovits T, Williamson PR, Williams DA, Fieberg A, Hullsiek KH, Abassi M, Dai B, Meya DB
Clin Infect Dis 2023 Dec 15;77(12):1659-1667. doi: 10.1093/cid/ciad440. PMID: 37606364Free PMC Article
Haeuser E, Serfes AL, Cork MA, Yang M, Abbastabar H, Abhilash ES, Adabi M, Adebayo OM, Adekanmbi V, Adeyinka DA, Afzal S, Ahinkorah BO, Ahmadi K, Ahmed MB, Akalu Y, Akinyemi RO, Akunna CJ, Alahdab F, Alanezi FM, Alanzi TM, Alene KA, Alhassan RK, Alipour V, Almasi-Hashiani A, Alvis-Guzman N, Ameyaw EK, Amini S, Amugsi DA, Ancuceanu R, Anvari D, Appiah SCY, Arabloo J, Aremu O, Asemahagn MA, Jafarabadi MA, Awedew AF, Quintanilla BPA, Ayanore MA, Aynalem YA, Azari S, Azene ZN, Darshan BB, Babalola TK, Baig AA, Banach M, Bärnighausen TW, Bell AW, Bhagavathula AS, Bhardwaj N, Bhardwaj P, Bhattacharyya K, Bijani A, Bitew ZW, Bohlouli S, Bolarinwa OA, Boloor A, Bozicevic I, Butt ZA, Cárdenas R, Carvalho F, Charan J, Chattu VK, Chowdhury MAK, Chu DT, Cowden RG, Dahlawi SMA, Damiani G, Darteh EKM, Darwesh AM, das Neves J, Weaver ND, De Leo D, De Neve JW, Deribe K, Deuba K, Dharmaratne S, Dianatinasab M, Diaz D, Didarloo A, Djalalinia S, Dorostkar F, Dubljanin E, Duko B, El Tantawi M, El-Jaafary SI, Eshrati B, Eskandarieh S, Eyawo O, Ezeonwumelu IJ, Ezzikouri S, Farzadfar F, Fattahi N, Fauk NK, Fernandes E, Filip I, Fischer F, Foigt NA, Foroutan M, Fukumoto T, Gad MM, Gaidhane AM, Gebregiorgis BG, Gebremedhin KB, Getacher L, Ghadiri K, Ghashghaee A, Golechha M, Gubari MIM, Gugnani HC, Guimarães RA, Haider MR, Haj-Mirzaian A, Hamidi S, Hashi A, Hassanipour S, Hassankhani H, Hayat K, Herteliu C, Ho HC, Holla R, Hosseini M, Hosseinzadeh M, Hwang BF, Ibitoye SE, Ilesanmi OS, Ilic IM, Ilic MD, Islam RM, Iwu CCD, Jakovljevic M, Jha RP, Ji JS, Johnson KB, Joseph N, Joshua V, Joukar F, Jozwiak JJ, Kalankesh LR, Kalhor R, Kamyari N, Kanchan T, Matin BK, Karimi SE, Kayode GA, Karyani AK, Keramati M, Khan EA, Khan G, Khan MN, Khatab K, Khubchandani J, Kim YJ, Kisa A, Kisa S, Kopec JA, Kosen S, Laxminarayana SLK, Koyanagi A, Krishan K, Defo BK, Kugbey N, Kulkarni V, Kumar M, Kumar N, Kusuma D, La Vecchia C, Lal DK, Landires I, Larson HJ, Lasrado S, Lee PH, Li S, Liu X, Maleki A, Malik P, Mansournia MA, Martins-Melo FR, Mendoza W, Menezes RG, Mengesha EW, Meretoja TJ, Mestrovic T, Mirica A, Moazen B, Mohamad O, Mohammad Y, Mohammadian-Hafshejani A, Mohammadpourhodki R, Mohammed S, Mohammed S, Mokdad AH, Moradi M, Moraga P, Mubarik S, Mulu GBB, Mwanri L, Nagarajan AJ, Naimzada MD, Naveed M, Nazari J, Ndejjo R, Negoi I, Ngalesoni FN, Nguefack-Tsague G, Ngunjiri JW, Nguyen CT, Nguyen HLT, Nnaji CA, Noubiap JJ, Nuñez-Samudio V, Nwatah VE, Oancea B, Odukoya OO, Olagunju AT, Olakunde BO, Olusanya BO, Olusanya JO, Bali AO, Onwujekwe OE, Orisakwe OE, Otstavnov N, Otstavnov SS, Owolabi MO, Mahesh PA, Padubidri JR, Pana A, Pandey A, Pandi-Perumal SR, Kan FP, Patton GC, Pawar S, Peprah EK, Postma MJ, Preotescu L, Syed ZQ, Rabiee N, Radfar A, Rafiei A, Rahim F, Rahimi-Movaghar V, Rahmani AM, Ramezanzadeh K, Rana J, Ranabhat CL, Rao SJ, Rawaf DL, Rawaf S, Rawassizadeh R, Regassa LD, Rezaei N, Rezapour A, Riaz MA, Ribeiro AI, Ross JM, Rubagotti E, Rumisha SF, Rwegerera GM, Moghaddam SS, Sagar R, Sahiledengle B, Sahu M, Salem MR, Kafil HS, Samy AM, Sartorius B, Sathian B, Seidu AA, Shaheen AA, Shaikh MA, Shamsizadeh M, Shiferaw WS, Shin JI, Shrestha R, Singh JA, Skryabin VY, Skryabina AA, Soltani S, Sufiyan MB, Tabuchi T, Tadesse EG, Taveira N, Tesfay FH, Thapar R, Tovani-Palone MR, Tsegaye GW, Umeokonkwo CD, Unnikrishnan B, Villafañe JH, Violante FS, Vo B, Vu GT, Wado YD, Waheed Y, Wamai RG, Wang Y, Ward P, Wickramasinghe ND, Wilson K, Yaya S, Yip P, Yonemoto N, Yu C, Zastrozhin MS, Zhang Y, Zhang ZJ, Hay SI, Dwyer-Lindgren L; Local Burden of Disease sub-Saharan Africa HIV Prevalence Collaborators
BMC Med 2022 Dec 19;20(1):488. doi: 10.1186/s12916-022-02639-z. PMID: 36529768Free PMC Article
Castle PE, Einstein MH, Sahasrabuddhe VV
CA Cancer J Clin 2021 Nov;71(6):505-526. Epub 2021 Sep 9 doi: 10.3322/caac.21696. PMID: 34499351Free PMC Article
McKay SL, Guo A, Pergam SA, Dooling K
Clin Infect Dis 2020 Oct 23;71(7):e125-e134. doi: 10.1093/cid/ciz1090. PMID: 31677266Free PMC Article
Nemes E, Geldenhuys H, Rozot V, Rutkowski KT, Ratangee F, Bilek N, Mabwe S, Makhethe L, Erasmus M, Toefy A, Mulenga H, Hanekom WA, Self SG, Bekker LG, Ryall R, Gurunathan S, DiazGranados CA, Andersen P, Kromann I, Evans T, Ellis RD, Landry B, Hokey DA, Hopkins R, Ginsberg AM, Scriba TJ, Hatherill M; C-040-404 Study Team
N Engl J Med 2018 Jul 12;379(2):138-149. doi: 10.1056/NEJMoa1714021. PMID: 29996082Free PMC Article

Diagnosis

Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV, Phan HTT, Hakim J, Johnson JL, Lourens M, Martinson NA, Muzanyi G, Narunsky K, Nerette S, Nguyen NV, Pham TH, Pierre S, Purfield AE, Samaneka W, Savic RM, Sanne I, Scott NA, Shenje J, Sizemore E, Vernon A, Waja Z, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group; Tuberculosis Trials Consortium
N Engl J Med 2021 May 6;384(18):1705-1718. doi: 10.1056/NEJMoa2033400. PMID: 33951360Free PMC Article
Nemes E, Geldenhuys H, Rozot V, Rutkowski KT, Ratangee F, Bilek N, Mabwe S, Makhethe L, Erasmus M, Toefy A, Mulenga H, Hanekom WA, Self SG, Bekker LG, Ryall R, Gurunathan S, DiazGranados CA, Andersen P, Kromann I, Evans T, Ellis RD, Landry B, Hokey DA, Hopkins R, Ginsberg AM, Scriba TJ, Hatherill M; C-040-404 Study Team
N Engl J Med 2018 Jul 12;379(2):138-149. doi: 10.1056/NEJMoa1714021. PMID: 29996082Free 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
Gershon AA, Breuer J, Cohen JI, Cohrs RJ, Gershon MD, Gilden D, Grose C, Hambleton S, Kennedy PG, Oxman MN, Seward JF, Yamanishi K
Nat Rev Dis Primers 2015 Jul 2;1:15016. doi: 10.1038/nrdp.2015.16. PMID: 27188665Free PMC Article
Dunmire SK, Hogquist KA, Balfour HH
Curr Top Microbiol Immunol 2015;390(Pt 1):211-40. doi: 10.1007/978-3-319-22822-8_9. PMID: 26424648Free PMC Article

Therapy

Boulware DR, Atukunda M, Kagimu E, Musubire AK, Akampurira A, Tugume L, Ssebambulidde K, Kasibante J, Nsangi L, Mugabi T, Gakuru J, Kimuda S, Kasozi D, Namombwe S, Turyasingura I, Rutakingirwa MK, Mpoza E, Kigozi E, Muzoora C, Ellis J, Skipper CP, Matkovits T, Williamson PR, Williams DA, Fieberg A, Hullsiek KH, Abassi M, Dai B, Meya DB
Clin Infect Dis 2023 Dec 15;77(12):1659-1667. doi: 10.1093/cid/ciad440. PMID: 37606364Free PMC Article
Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV, Phan HTT, Hakim J, Johnson JL, Lourens M, Martinson NA, Muzanyi G, Narunsky K, Nerette S, Nguyen NV, Pham TH, Pierre S, Purfield AE, Samaneka W, Savic RM, Sanne I, Scott NA, Shenje J, Sizemore E, Vernon A, Waja Z, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group; Tuberculosis Trials Consortium
N Engl J Med 2021 May 6;384(18):1705-1718. doi: 10.1056/NEJMoa2033400. PMID: 33951360Free PMC Article
Nemes E, Geldenhuys H, Rozot V, Rutkowski KT, Ratangee F, Bilek N, Mabwe S, Makhethe L, Erasmus M, Toefy A, Mulenga H, Hanekom WA, Self SG, Bekker LG, Ryall R, Gurunathan S, DiazGranados CA, Andersen P, Kromann I, Evans T, Ellis RD, Landry B, Hokey DA, Hopkins R, Ginsberg AM, Scriba TJ, Hatherill M; C-040-404 Study Team
N Engl J Med 2018 Jul 12;379(2):138-149. doi: 10.1056/NEJMoa1714021. PMID: 29996082Free 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
Gershon AA, Breuer J, Cohen JI, Cohrs RJ, Gershon MD, Gilden D, Grose C, Hambleton S, Kennedy PG, Oxman MN, Seward JF, Yamanishi K
Nat Rev Dis Primers 2015 Jul 2;1:15016. doi: 10.1038/nrdp.2015.16. PMID: 27188665Free PMC Article

Prognosis

Malagón T, Franco EL, Tejada R, Vaccarella S
Nat Rev Clin Oncol 2024 Jul;21(7):522-538. Epub 2024 May 17 doi: 10.1038/s41571-024-00904-z. PMID: 38760499
Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV, Phan HTT, Hakim J, Johnson JL, Lourens M, Martinson NA, Muzanyi G, Narunsky K, Nerette S, Nguyen NV, Pham TH, Pierre S, Purfield AE, Samaneka W, Savic RM, Sanne I, Scott NA, Shenje J, Sizemore E, Vernon A, Waja Z, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group; Tuberculosis Trials Consortium
N Engl J Med 2021 May 6;384(18):1705-1718. doi: 10.1056/NEJMoa2033400. PMID: 33951360Free PMC Article
McKay SL, Guo A, Pergam SA, Dooling K
Clin Infect Dis 2020 Oct 23;71(7):e125-e134. doi: 10.1093/cid/ciz1090. PMID: 31677266Free PMC Article
Tait DR, Hatherill M, Van Der Meeren O, Ginsberg AM, Van Brakel E, Salaun B, Scriba TJ, Akite EJ, Ayles HM, Bollaerts A, Demoitié MA, Diacon A, Evans TG, Gillard P, Hellström E, Innes JC, Lempicki M, Malahleha M, Martinson N, Mesia Vela D, Muyoyeta M, Nduba V, Pascal TG, Tameris M, Thienemann F, Wilkinson RJ, Roman F
N Engl J Med 2019 Dec 19;381(25):2429-2439. Epub 2019 Oct 29 doi: 10.1056/NEJMoa1909953. PMID: 31661198
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

Clinical prediction guides

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
Egan K, Hook LM, LaTourette P, Desmond A, Awasthi S, Friedman HM
Transl Res 2020 Jun;220:138-152. Epub 2020 Mar 16 doi: 10.1016/j.trsl.2020.03.004. PMID: 32272093Free PMC Article
Nemes E, Geldenhuys H, Rozot V, Rutkowski KT, Ratangee F, Bilek N, Mabwe S, Makhethe L, Erasmus M, Toefy A, Mulenga H, Hanekom WA, Self SG, Bekker LG, Ryall R, Gurunathan S, DiazGranados CA, Andersen P, Kromann I, Evans T, Ellis RD, Landry B, Hokey DA, Hopkins R, Ginsberg AM, Scriba TJ, Hatherill M; C-040-404 Study Team
N Engl J Med 2018 Jul 12;379(2):138-149. doi: 10.1056/NEJMoa1714021. PMID: 29996082Free 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
Egberink H, Horzinek MC
Vet Microbiol 1992 Nov;33(1-4):311-31. doi: 10.1016/0378-1135(92)90059-3. PMID: 1336243Free PMC Article

Recent systematic reviews

Griffin DWJ, Pai Mangalore R, Hoy JF, McMahon JH
AIDS 2023 Jul 15;37(9):1345-1360. Epub 2023 Apr 13 doi: 10.1097/QAD.0000000000003579. PMID: 37070539Free PMC Article
Drzymalla E, Green RF, Knuth M, Khoury MJ, Dotson WD, Gundlapalli A
Clin Immunol 2022 Oct;243:109097. Epub 2022 Aug 13 doi: 10.1016/j.clim.2022.109097. PMID: 35973637Free PMC Article
McKay SL, Guo A, Pergam SA, Dooling K
Clin Infect Dis 2020 Oct 23;71(7):e125-e134. doi: 10.1093/cid/ciz1090. PMID: 31677266Free PMC Article
Shaghaghi M, Soleyman-Jahi S, Abolhassani H, Yazdani R, Azizi G, Rezaei N, Barbouche MR, McKinlay MA, Aghamohammadi A
Vaccine 2018 Mar 20;36(13):1711-1719. Epub 2018 Feb 23 doi: 10.1016/j.vaccine.2018.02.059. PMID: 29478755
Guo J, Bolivar-Wagers S, Srinivas N, Holubar M, Maldonado Y
Vaccine 2015 Mar 3;33(10):1235-42. Epub 2015 Jan 16 doi: 10.1016/j.vaccine.2015.01.018. PMID: 25600519Free PMC Article

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