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Agammaglobulinemia 9, autosomal recessive(AGM9)

MedGen UID:
1794269
•Concept ID:
C5562059
•
Disease or Syndrome
Synonyms: AGAMMAGLOBULINEMIA, AUTOSOMAL RECESSIVE, DUE TO SLC39A7 DEFECT; AGM9
 
Gene (location): SLC39A7 (6p21.32)
 
Monarch Initiative: MONDO:0030519
OMIM®: 619693

Definition

Agammaglobulinemia-9 (AGM9) is an autosomal recessive primary immunodeficiency characterized by recurrent bacterial infections associated with agammaglobulinemia and absence of circulating B cells. Additional features include failure to thrive and skin involvement. The severity is variable: more severe cases may require hematopoietic stem cell transplantation, whereas others can be treated effectively with Ig replacement therapy (summary by Anzilotti et al., 2019). For a discussion of genetic heterogeneity of autosomal agammaglobulinemia, see AGM1 (601495). [from OMIM]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
•Concept ID:
C2315100
•
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
See: Feature record | Search on this feature
Sensorineural hearing loss disorder
MedGen UID:
9164
•Concept ID:
C0018784
•
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
See: Feature record | Search on this feature
Thrombocytopenia
MedGen UID:
52737
•Concept ID:
C0040034
•
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
See: Feature record | Search on this feature
Agammaglobulinemia
MedGen UID:
168
•Concept ID:
C0001768
•
Disease or Syndrome
A lasting absence of total IgG and total IgA and total IgM in the blood circulation, whereby at most trace quantities can be measured.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Seborrheic dermatitis
MedGen UID:
19912
•Concept ID:
C0036508
•
Disease or Syndrome
Seborrheic dermatitis is a form of eczema which is closely related to dandruff. It causes dry or greasy peeling of the scalp, eyebrows, and face, and sometimes trunk.
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Recurrent bacterial infections
MedGen UID:
334943
•Concept ID:
C1844383
•
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.
See: Feature record | Search on this feature
Absent circulating B cells
MedGen UID:
868166
•Concept ID:
C4022558
•
Finding
Complete lack of mature B cells, that is, of B cells that have left the bone marrow.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Agammaglobulinemia: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management.
Pashangzadeh S, Yazdani R, Nazari F, Azizi G, Abolhassani H, Aghamohammadi A
Endocr Metab Immune Disord Drug Targets 2020;20(9):1434-1447. doi: 10.2174/1871530320666200508114349. PMID: 32384040

Recent clinical studies

Etiology

A Monogenic Disease with a Variety of Phenotypes: Deficiency of Adenosine Deaminase 2.
Özen S, Batu ED, Taşkıran EZ, Özkara HA, Ünal Ş, Güleray N, Erden A, Karadağ Ö, Gümrük F, Çetin M, Sönmez HE, Bilginer Y, Ayvaz DÇ, Tezcan I
J Rheumatol 2020 Jan;47(1):117-125. Epub 2019 May 1 doi: 10.3899/jrheum.181384. PMID: 31043544
Molecular analysis of a large cohort of patients with the hyper immunoglobulin M (IgM) syndrome.
Lee WI, Torgerson TR, Schumacher MJ, Yel L, Zhu Q, Ochs HD
Blood 2005 Mar 1;105(5):1881-90. Epub 2004 Sep 9 doi: 10.1182/blood-2003-12-4420. PMID: 15358621
A new case of autosomal recessive agammaglobulinaemia with impaired pre-B cell differentiation due to a large deletion of the IGH locus.
Milili M, Antunes H, Blanco-Betancourt C, Nogueiras A, Santos E, Vasconcelos J, Castro e Melo J, Schiff C
Eur J Pediatr 2002 Sep;161(9):479-84. Epub 2002 Jul 12 doi: 10.1007/s00431-002-0994-9. PMID: 12200606

Diagnosis

Case Report: Consistent disease manifestations with a staggered time course in two identical twins affected by adenosine deaminase 2 deficiency.
Barzaghi F, Cicalese MP, Zoccolillo M, Brigida I, Barcella M, Merelli I, Sartirana C, Zanussi M, Calbi V, Bernardo ME, Tucci F, Migliavacca M, Giglio F, Doglio M, Canarutto D, Ferrua F, Consiglieri G, Prunotto G, Saettini F, Bonanomi S, Rovere-Querini P, Di Colo G, Jofra T, Fousteri G, Penco F, Gattorno M, Hershfield MS, Bongiovanni L, Ponzoni M, Marktel S, Milani R, Peccatori J, Ciceri F, Mortellaro A, Aiuti A
Front Immunol 2022;13:910021. Epub 2022 Sep 29 doi: 10.3389/fimmu.2022.910021. PMID: 36248833Free PMC Article
Case Report: Susceptibility to viral infections and secondary hemophagocytic lymphohistiocytosis responsive to intravenous immunoglobulin as primary manifestations of adenosine deaminase 2 deficiency.
Drago E, Garbarino F, Signa S, Grossi A, Schena F, Penco F, Santori E, Candotti F, Boztug K, Volpi S, Gattorno M, Caorsi R
Front Immunol 2022;13:937108. Epub 2022 Sep 9 doi: 10.3389/fimmu.2022.937108. PMID: 36159847Free PMC Article
Agammaglobulinemia: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management.
Pashangzadeh S, Yazdani R, Nazari F, Azizi G, Abolhassani H, Aghamohammadi A
Endocr Metab Immune Disord Drug Targets 2020;20(9):1434-1447. doi: 10.2174/1871530320666200508114349. PMID: 32384040
ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome.
Cagdas D, Gur Cetinkaya P, Karaatmaca B, Esenboga S, Tan C, Yılmaz T, Gümüş E, Barış S, Kuşkonmaz B, Ozgur TT, Bali P, Santisteban I, Orhan D, Yüce A, Cetinkaya D, Boztug K, Hershfield M, Sanal O, Tezcan İ
J Clin Immunol 2018 May;38(4):484-493. Epub 2018 May 9 doi: 10.1007/s10875-018-0496-9. PMID: 29744787
Molecular analysis of a large cohort of patients with the hyper immunoglobulin M (IgM) syndrome.
Lee WI, Torgerson TR, Schumacher MJ, Yel L, Zhu Q, Ochs HD
Blood 2005 Mar 1;105(5):1881-90. Epub 2004 Sep 9 doi: 10.1182/blood-2003-12-4420. PMID: 15358621

Therapy

Case Report: Susceptibility to viral infections and secondary hemophagocytic lymphohistiocytosis responsive to intravenous immunoglobulin as primary manifestations of adenosine deaminase 2 deficiency.
Drago E, Garbarino F, Signa S, Grossi A, Schena F, Penco F, Santori E, Candotti F, Boztug K, Volpi S, Gattorno M, Caorsi R
Front Immunol 2022;13:937108. Epub 2022 Sep 9 doi: 10.3389/fimmu.2022.937108. PMID: 36159847Free PMC Article
Agammaglobulinemia: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management.
Pashangzadeh S, Yazdani R, Nazari F, Azizi G, Abolhassani H, Aghamohammadi A
Endocr Metab Immune Disord Drug Targets 2020;20(9):1434-1447. doi: 10.2174/1871530320666200508114349. PMID: 32384040
Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency.
Cicalese MP, Ferrua F, Castagnaro L, Pajno R, Barzaghi F, Giannelli S, Dionisio F, Brigida I, Bonopane M, Casiraghi M, Tabucchi A, Carlucci F, Grunebaum E, Adeli M, Bredius RG, Puck JM, Stepensky P, Tezcan I, Rolfe K, De Boever E, Reinhardt RR, Appleby J, Ciceri F, Roncarolo MG, Aiuti A
Blood 2016 Jul 7;128(1):45-54. Epub 2016 Apr 29 doi: 10.1182/blood-2016-01-688226. PMID: 27129325Free PMC Article

Prognosis

Case Report: Consistent disease manifestations with a staggered time course in two identical twins affected by adenosine deaminase 2 deficiency.
Barzaghi F, Cicalese MP, Zoccolillo M, Brigida I, Barcella M, Merelli I, Sartirana C, Zanussi M, Calbi V, Bernardo ME, Tucci F, Migliavacca M, Giglio F, Doglio M, Canarutto D, Ferrua F, Consiglieri G, Prunotto G, Saettini F, Bonanomi S, Rovere-Querini P, Di Colo G, Jofra T, Fousteri G, Penco F, Gattorno M, Hershfield MS, Bongiovanni L, Ponzoni M, Marktel S, Milani R, Peccatori J, Ciceri F, Mortellaro A, Aiuti A
Front Immunol 2022;13:910021. Epub 2022 Sep 29 doi: 10.3389/fimmu.2022.910021. PMID: 36248833Free PMC Article
Agammaglobulinemia: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management.
Pashangzadeh S, Yazdani R, Nazari F, Azizi G, Abolhassani H, Aghamohammadi A
Endocr Metab Immune Disord Drug Targets 2020;20(9):1434-1447. doi: 10.2174/1871530320666200508114349. PMID: 32384040
Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency.
Cicalese MP, Ferrua F, Castagnaro L, Pajno R, Barzaghi F, Giannelli S, Dionisio F, Brigida I, Bonopane M, Casiraghi M, Tabucchi A, Carlucci F, Grunebaum E, Adeli M, Bredius RG, Puck JM, Stepensky P, Tezcan I, Rolfe K, De Boever E, Reinhardt RR, Appleby J, Ciceri F, Roncarolo MG, Aiuti A
Blood 2016 Jul 7;128(1):45-54. Epub 2016 Apr 29 doi: 10.1182/blood-2016-01-688226. PMID: 27129325Free PMC Article
Fatal adult-onset antibody deficiency syndrome in a patient with cartilage hair hypoplasia.
Horn J, Schlesier M, Warnatz K, Prasse A, Superti-Furga A, Peter HH, Salzer U
Hum Immunol 2010 Sep;71(9):916-9. Epub 2010 Jun 9 doi: 10.1016/j.humimm.2010.06.002. PMID: 20538026
Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome).
Hagleitner MM, Lankester A, Maraschio P, Hultén M, Fryns JP, Schuetz C, Gimelli G, Davies EG, Gennery A, Belohradsky BH, de Groot R, Gerritsen EJ, Mattina T, Howard PJ, Fasth A, Reisli I, Furthner D, Slatter MA, Cant AJ, Cazzola G, van Dijken PJ, van Deuren M, de Greef JC, van der Maarel SM, Weemaes CM
J Med Genet 2008 Feb;45(2):93-9. Epub 2007 Sep 24 doi: 10.1136/jmg.2007.053397. PMID: 17893117

Clinical prediction guides

Case Report: Consistent disease manifestations with a staggered time course in two identical twins affected by adenosine deaminase 2 deficiency.
Barzaghi F, Cicalese MP, Zoccolillo M, Brigida I, Barcella M, Merelli I, Sartirana C, Zanussi M, Calbi V, Bernardo ME, Tucci F, Migliavacca M, Giglio F, Doglio M, Canarutto D, Ferrua F, Consiglieri G, Prunotto G, Saettini F, Bonanomi S, Rovere-Querini P, Di Colo G, Jofra T, Fousteri G, Penco F, Gattorno M, Hershfield MS, Bongiovanni L, Ponzoni M, Marktel S, Milani R, Peccatori J, Ciceri F, Mortellaro A, Aiuti A
Front Immunol 2022;13:910021. Epub 2022 Sep 29 doi: 10.3389/fimmu.2022.910021. PMID: 36248833Free PMC Article
ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome.
Cagdas D, Gur Cetinkaya P, Karaatmaca B, Esenboga S, Tan C, Yılmaz T, Gümüş E, Barış S, Kuşkonmaz B, Ozgur TT, Bali P, Santisteban I, Orhan D, Yüce A, Cetinkaya D, Boztug K, Hershfield M, Sanal O, Tezcan İ
J Clin Immunol 2018 May;38(4):484-493. Epub 2018 May 9 doi: 10.1007/s10875-018-0496-9. PMID: 29744787

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