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Immunodeficiency 62(IMD62)

MedGen UID:: 1673905
•Concept ID:: C5193109
•: Disease or Syndrome

Synonyms:	IMD62; IMMUNODEFICIENCY 62

Gene (location): Gene(s) directly associated with this condition or phenotype.	ARHGEF1 (19q13.2)

Monarch Initiative:	MONDO:0032763
OMIM®:	618459

Definition

Immunodeficiency-62 (IMD62) is an autosomal recessive primary immunologic disorder clinically characterized by onset of recurrent upper and lower respiratory infections late in the first decade of life. Patients may also have increased viral susceptibility to varicella zoster virus (VZV) or herpes simplex virus (HSV). Laboratory studies show impaired antibody response to vaccination, low levels of circulating memory B cells, and almost undetectable antibodies. There is also evidence of secondary T-cell dysfunction. The disorder may result from disturbed actin cytoskeleton dynamics causing impaired lymphocyte migration (summary by Bouafia et al., 2019). [from OMIM]

Clinical features

From HPO

Bronchiectasis

MedGen UID:: 14234
•Concept ID:: C0006267
•: Disease or Syndrome

Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.

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Recurrent upper respiratory tract infections

MedGen UID:: 154380
•Concept ID:: C0581381
•: Disease or Syndrome

An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).

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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.

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Decreased circulating total IgM

MedGen UID:: 116095
•Concept ID:: C0239989
•: Finding

An abnormally decreased level of immunoglobulin M (IgM) in blood.

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Autoimmune thrombocytopenia

MedGen UID:: 116621
•Concept ID:: C0242584
•: Disease or Syndrome

The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.

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Varicella, severe recurrent

MedGen UID:: 322202
•Concept ID:: C1833487
•: Disease or Syndrome

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B lymphocytopenia

MedGen UID:: 340780
•Concept ID:: C1855067
•: Finding

An abnormal decrease from the normal count of B cells.

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Recurrent herpes

MedGen UID:: 870750
•Concept ID:: C4025207
•: Finding

Increased susceptibility to herpesvirus, as manifested by recurrent episodes of herpesvirus.

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Decreased proportion of memory B cells

MedGen UID:: 893145
•Concept ID:: C4072913
•: Finding

A reduction in the normal proportion of memory B cells (CD19+/CD27+) in circulation relative to the total number of B cells. Memory B cells develop from naive B cells. Upon antigen rechallenge, memory B cells rapidly expand and differentiate into plasma cells under the cognate control of memory Th cells (Phase IV).

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Increased proportion of transitional B cells

MedGen UID:: 892766
•Concept ID:: C4072920
•: Finding

An elevation in the normal proportion of transitional B cells (CD19+/CD38high/IgMhigh) in circulation relative to the total number of B cells. B cells originate from precursors in the bone marrow, and the first cells which migrate to the peripheral blood have been classified as transitional B cells.

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Reduced isohemagglutinin level

MedGen UID:: 1700218
•Concept ID:: C5139157
•: Finding

Level of isohemagglutinin reduced below expected concentration. An isohemagglutinin refers to the naturally occurring antibodies in the ABO blood group system (i.e., anti-A in a group B person, anti-B in a group A person, and anti-A, anti-B, and anti-A,B in a group O person).

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Complete or near-complete absence of specific antibody response to tetanus vaccine

MedGen UID:: 1687415
•Concept ID:: C5139458
•: Finding

The inability to synthesize postvaccination antibodies against a tetanus antigen, as measured by antibody titer determination following vaccination.

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Decreased circulating IgG concentration

MedGen UID:: 1720114
•Concept ID:: C5234937
•: Finding

An abnormally decreased level of immunoglobulin G (IgG) in blood.

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Abnormality of the immune system
Abnormality of the respiratory system

Professional guidelines

PubMed

Survival in primary hemophagocytic lymphohistiocytosis, 2016 to 2021: etoposide is better than its reputation.

Böhm S, Wustrau K, Pachlopnik Schmid J, Prader S, Ahlmann M, Yacobovich J, Beier R, Speckmann C, Behnisch W, Ifversen M, Jordan M, Marsh R, Naumann-Bartsch N, Mauz-Körholz C, Hönig M, Schulz A, Malinowska I, Hines M, Nichols KE, Gil-Herrera J, Talano JA, Crooks B, Formankova R, Jorch N, Bakhtiar S, Kühnle I, Streiter M, Nathrath M, Russo A, Dürken M, Lang P, Lindemans C, Henter JI, Lehmberg K, Ehl S
Blood 2024 Mar 7;143(10):872-881. doi: 10.1182/blood.2023022281. PMID: 37992218

Ibrutinib does not reverse disease- and treatment-related hypogammaglobulinaemia associated with chronic lymphocytic leukemia.

Khan S, Durairaj S, Phumphukhieo P, Holding S, Allsup D
Leuk Lymphoma 2021 Jul;62(7):1786-1789. Epub 2021 Feb 17 doi: 10.1080/10428194.2021.1885662. PMID: 33596758

Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects.

Schwab C, Gabrysch A, Olbrich P, Patiño V, Warnatz K, Wolff D, Hoshino A, Kobayashi M, Imai K, Takagi M, Dybedal I, Haddock JA, Sansom DM, Lucena JM, Seidl M, Schmitt-Graeff A, Reiser V, Emmerich F, Frede N, Bulashevska A, Salzer U, Schubert D, Hayakawa S, Okada S, Kanariou M, Kucuk ZY, Chapdelaine H, Petruzelkova L, Sumnik Z, Sediva A, Slatter M, Arkwright PD, Cant A, Lorenz HM, Giese T, Lougaris V, Plebani A, Price C, Sullivan KE, Moutschen M, Litzman J, Freiberger T, van de Veerdonk FL, Recher M, Albert MH, Hauck F, Seneviratne S, Pachlopnik Schmid J, Kolios A, Unglik G, Klemann C, Speckmann C, Ehl S, Leichtner A, Blumberg R, Franke A, Snapper S, Zeissig S, Cunningham-Rundles C, Giulino-Roth L, Elemento O, Dückers G, Niehues T, Fronkova E, Kanderová V, Platt CD, Chou J, Chatila TA, Geha R, McDermott E, Bunn S, Kurzai M, Schulz A, Alsina L, Casals F, Deyà-Martinez A, Hambleton S, Kanegane H, Taskén K, Neth O, Grimbacher B
J Allergy Clin Immunol 2018 Dec;142(6):1932-1946. Epub 2018 May 4 doi: 10.1016/j.jaci.2018.02.055. PMID: 29729943 Free PMC Article

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Recent clinical studies

Etiology

The monogenic landscape of human infectious diseases.

Boisson-Dupuis S, Bastard P, Béziat V, Bustamante J, Cobat A, Jouanguy E, Puel A, Rosain J, Zhang Q, Zhang SY, Boisson B
J Allergy Clin Immunol 2025 Mar;155(3):768-783. Epub 2024 Dec 24 doi: 10.1016/j.jaci.2024.12.1078. PMID: 39724971 Free PMC Article

Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.

Leiding JW, Vogel TP, Santarlas VGJ, Mhaskar R, Smith MR, Carisey A, Vargas-Hernández A, Silva-Carmona M, Heeg M, Rensing-Ehl A, Neven B, Hadjadj J, Hambleton S, Ronan Leahy T, Meesilpavikai K, Cunningham-Rundles C, Dutmer CM, Sharapova SO, Taskinen M, Chua I, Hague R, Klemann C, Kostyuchenko L, Morio T, Thatayatikom A, Ozen A, Scherbina A, Bauer CS, Flanagan SE, Gambineri E, Giovannini-Chami L, Heimall J, Sullivan KE, Allenspach E, Romberg N, Deane SG, Prince BT, Rose MJ, Bohnsack J, Mousallem T, Jesudas R, Santos Vilela MMD, O'Sullivan M, Pachlopnik Schmid J, Průhová Š, Klocperk A, Rees M, Su H, Bahna S, Baris S, Bartnikas LM, Chang Berger A, Briggs TA, Brothers S, Bundy V, Chan AY, Chandrakasan S, Christiansen M, Cole T, Cook MC, Desai MM, Fischer U, Fulcher DA, Gallo S, Gauthier A, Gennery AR, Gonçalo Marques J, Gottrand F, Grimbacher B, Grunebaum E, Haapaniemi E, Hämäläinen S, Heiskanen K, Heiskanen-Kosma T, Hoffman HM, Gonzalez-Granado LI, Guerrerio AL, Kainulainen L, Kumar A, Lawrence MG, Levin C, Martelius T, Neth O, Olbrich P, Palma A, Patel NC, Pozos T, Preece K, Lugo Reyes SO, Russell MA, Schejter Y, Seroogy C, Sinclair J, Skevofilax E, Suan D, Suez D, Szabolcs P, Velasco H, Warnatz K, Walkovich K, Worth A; STAT3 GOF Working Group members, Seppänen MRJ, Torgerson TR, Sogkas G, Ehl S, Tangye SG, Cooper MA, Milner JD, Forbes Satter LR
J Allergy Clin Immunol 2023 Apr;151(4):1081-1095. Epub 2022 Oct 11 doi: 10.1016/j.jaci.2022.09.002. PMID: 36228738 Free PMC Article

Lateral flow urine lipoarabinomannan assay for extrapulmonary tuberculosis diagnosis in adults who are HIV-positive.

Indirawati NN, Yunihastuti E, Yulianti M, Nasir UZ, Wulandari D, Rinaldi I
Int J Infect Dis 2022 Sep;122:415-419. Epub 2022 Jun 8 doi: 10.1016/j.ijid.2022.06.007. PMID: 35690363

Waldenström macroglobulinemia and relationship to immune deficiency.

Levy A, Guidez S, Debiais C, Princet I, Bouyer S, Dindinaud E, Delwail V, Systchenko T, Moya N, Gruchet C, Sabirou F, Bobin A, Gardeney H, Nsiala L, Cailly L, Olivier G, Motard C, Fleck E, Corby A, Roul C, Denis G, Dieval C, Leleu X, Tomowiak C
Leuk Lymphoma 2021 Nov;62(11):2665-2670. Epub 2021 Jun 4 doi: 10.1080/10428194.2021.1907379. PMID: 34085595

Important differences in the diagnostic spectrum of primary immunodeficiency in adults versus children.

Abolhassani H, Rezaei N, Mohammadinejad P, Mirminachi B, Hammarstrom L, Aghamohammadi A
Expert Rev Clin Immunol 2015 Feb;11(2):289-302. Epub 2015 Jan 5 doi: 10.1586/1744666X.2015.990440. PMID: 25556968

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Diagnosis

The monogenic landscape of human infectious diseases.

Mpox in people with advanced HIV infection: a global case series.

Mitjà O, Alemany A, Marks M, Lezama Mora JI, Rodríguez-Aldama JC, Torres Silva MS, Corral Herrera EA, Crabtree-Ramirez B, Blanco JL, Girometti N, Mazzotta V, Hazra A, Silva M, Montenegro-Idrogo JJ, Gebo K, Ghosn J, Peña Vázquez MF, Matos Prado E, Unigwe U, Villar-García J, Wald-Dickler N, Zucker J, Paredes R, Calmy A, Waters L, Galvan-Casas C, Walmsley S, Orkin CM; SHARE-NET writing group
Lancet 2023 Mar 18;401(10380):939-949. Epub 2023 Feb 21 doi: 10.1016/S0140-6736(23)00273-8. PMID: 36828001

Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.

Waldenström macroglobulinemia and relationship to immune deficiency.

Approach to Children with Recurrent Infections.

Hernandez-Trujillo VP
Immunol Allergy Clin North Am 2015 Nov;35(4):625-36. Epub 2015 Sep 4 doi: 10.1016/j.iac.2015.07.005. PMID: 26454310

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Therapy

Optimizing behavioral and pharmacological smoking cessation interventions among people with HIV.

Himelhoch S, Kelly D, deFilippi C, Taylor G, Bennett M, Medoff D, Li L, Christenson R, Potts W, Shuter J
AIDS 2024 Apr 1;38(5):669-678. Epub 2023 Dec 20 doi: 10.1097/QAD.0000000000003821. PMID: 38126353

Adherence to antiretroviral therapy and factors associated with non-adherence: a cohort study at two referral services in Brazil.

Fonseca Lima RA, Miranda-Filho DB, Montarroyos UR, Cavalcanti ATAE, Ximenes RAA
AIDS Care 2023 Jul;35(7):961-969. Epub 2022 Jan 31 doi: 10.1080/09540121.2022.2029814. PMID: 35100884

The clinical development process for a novel preventive vaccine: An overview.

Singh K, Mehta S
J Postgrad Med 2016 Jan-Mar;62(1):4-11. doi: 10.4103/0022-3859.173187. PMID: 26732191 Free PMC Article

A review of factors influencing the incidence and severity of plaque-induced gingivitis.

Trombelli L, Farina R
Minerva Stomatol 2013 Jun;62(6):207-34. PMID: 23828258

Pulmonary candidosis.

Arthur LJ
Proc R Soc Med 1969 Sep;62(9):906-7. PMID: 5823808 Free PMC Article

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Prognosis

Waldenström macroglobulinemia and relationship to immune deficiency.

Convalescent hyperimmune plasma for chemo-immunotherapy induced immunodeficiency in COVID-19 patients with hematological malignancies.

Ferrari S, Caprioli C, Weber A, Rambaldi A, Lussana F
Leuk Lymphoma 2021 Jun;62(6):1490-1496. Epub 2021 Jan 18 doi: 10.1080/10428194.2021.1872070. PMID: 33461387 Free PMC Article

Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV: Systematic Review and Meta-Analysis.

Shah ASV, Stelzle D, Lee KK, Beck EJ, Alam S, Clifford S, Longenecker CT, Strachan F, Bagchi S, Whiteley W, Rajagopalan S, Kottilil S, Nair H, Newby DE, McAllister DA, Mills NL
Circulation 2018 Sep 11;138(11):1100-1112. doi: 10.1161/CIRCULATIONAHA.117.033369. PMID: 29967196 Free PMC Article

A review of factors influencing the incidence and severity of plaque-induced gingivitis.

Trombelli L, Farina R
Minerva Stomatol 2013 Jun;62(6):207-34. PMID: 23828258

Estimating HIV incidence among female partners of bisexual men in China.

Chow EP, Wilson DP, Zhang L
Int J Infect Dis 2012 May;16(5):e312-20. Epub 2012 Mar 20 doi: 10.1016/j.ijid.2012.01.012. PMID: 22440544

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Clinical prediction guides

Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.

Clinical Predictors of Liver Fibrosis Presence and Progression in Human Immunodeficiency Virus-Associated Nonalcoholic Fatty Liver Disease.

Fourman LT, Stanley TL, Zheng I, Pan CS, Feldpausch MN, Purdy J, Aepfelbacher J, Buckless C, Tsao A, Corey KE, Chung RT, Torriani M, Kleiner DE, Hadigan CM, Grinspoon SK
Clin Infect Dis 2021 Jun 15;72(12):2087-2094. doi: 10.1093/cid/ciaa382. PMID: 32270862 Free PMC Article

Predictors of cure among HIV co-infected multidrug-resistant TB patients at Sizwe Tropical Disease Hospital Johannesburg, South Africa.

Umanah TA, Ncayiyana JR, Nyasulu PS
Trans R Soc Trop Med Hyg 2015 May;109(5):340-8. Epub 2015 Mar 18 doi: 10.1093/trstmh/trv025. PMID: 25787727

A review of factors influencing the incidence and severity of plaque-induced gingivitis.

Trombelli L, Farina R
Minerva Stomatol 2013 Jun;62(6):207-34. PMID: 23828258

Assessing and achieving readiness to initiate HIV medication.

Nordqvist O, Södergård B, Tully MP, Sönnerborg A, Lindblad AK
Patient Educ Couns 2006 Jul;62(1):21-30. doi: 10.1016/j.pec.2005.09.014. PMID: 16766244

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Recent systematic reviews

The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.

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Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV: Systematic Review and Meta-Analysis.

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Immunodeficiency 62(IMD62)

Definition

Clinical features

Professional guidelines

PubMed

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Recent systematic reviews

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Practice guidelines

Molecular resources

Consumer resources

Reviews

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