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Hyper-IgM syndrome type 5(HIGM5)

MedGen UID:
328420
•Concept ID:
C1720958
•
Disease or Syndrome
Synonyms: HIGM5; Hyper-IgM Immunodeficiency Syndrome, Type 5; Immunodeficiency with hyper IgM type 5
 
Gene (location): UNG (12q24.11)
 
Monarch Initiative: MONDO:0011971
OMIM®: 608106
Orphanet: ORPHA101092

Definition

Hyper-IgM syndrome is a condition characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations, indicating a defect in the class-switch recombination (CSR) process. For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230). [from OMIM]

Clinical features

From HPO
Recurrent upper and lower respiratory tract infections
MedGen UID:
375014
•Concept ID:
C1842777
•
Finding
Increased susceptibility to upper and lower respiratory tract infections, as manifested by recurrent episodes of upper and lower respiratory tract infections.
See: Feature record | Search on this feature
Epididymitis
MedGen UID:
4986
•Concept ID:
C0014534
•
Disease or Syndrome
The presence of inflammation of the epididymis.
See: Feature record | Search on this feature
Immunodeficiency
MedGen UID:
7034
•Concept ID:
C0021051
•
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
See: Feature record | Search on this feature
Decreased circulating IgA level
MedGen UID:
57934
•Concept ID:
C0162538
•
Disease or Syndrome
Decreased levels of immunoglobulin A (IgA).
See: Feature record | Search on this feature
Lymphadenopathy
MedGen UID:
96929
•Concept ID:
C0497156
•
Disease or Syndrome
Enlargment (swelling) of a lymph node.
See: Feature record | Search on this feature
Increased circulating IgM level
MedGen UID:
333454
•Concept ID:
C1839972
•
Finding
An abnormally increased level of immunoglobulin M in blood.
See: Feature record | Search on this feature
Impaired Ig class switch recombination
MedGen UID:
374953
•Concept ID:
C1842528
•
Finding
An impairment of the class-switch recombination process that normally leads B lymphocytes to produce IgG, IgA, or IgE.
See: Feature record | Search on this feature
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
Decreased circulating IgG level
MedGen UID:
1720114
•Concept ID:
C5234937
•
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHyper-IgM syndrome type 5
Follow this link to review classifications for Hyper-IgM syndrome type 5 in Orphanet.

Professional guidelines

PubMed

Complex preimplantation genetic tests for Robertsonian translocation, HLA, and X-linked hyper IgM syndrome caused by a novel mutation of CD40LG gene.
Huang S, Niu Y, Li J, Gao M, Zhang Y, Yan J, Ma S, Gao X, Gao Y
J Assist Reprod Genet 2020 Aug;37(8):2025-2031. Epub 2020 Jun 5 doi: 10.1007/s10815-020-01846-y. PMID: 32500460Free PMC Article
CD40 ligand deficiency: treatment strategies and novel therapeutic perspectives.
França TT, Barreiros LA, Al-Ramadi BK, Ochs HD, Cabral-Marques O, Condino-Neto A
Expert Rev Clin Immunol 2019 May;15(5):529-540. Epub 2019 Feb 18 doi: 10.1080/1744666X.2019.1573674. PMID: 30681380
Patients with abnormal IgM levels: assessment, clinical interpretation, and treatment.
Ochs HD
Ann Allergy Asthma Immunol 2008 May;100(5):509-11. doi: 10.1016/S1081-1206(10)60479-6. PMID: 18517086

Recent clinical studies

Etiology

Pulmonary Radiological Manifestations of Humoral and Combined Immunodeficiencies in a Tertiary Pediatric Center.
Khalili M, Farzi H, Darougar S, Hajijoo F, Mesdaghi M, Mansouri M, Babaie D, Hashemitari A, Eslami N, Chavoshzadeh Z
Iran J Allergy Asthma Immunol 2021 Dec 8;20(6):693-699. doi: 10.18502/ijaai.v20i6.8020. PMID: 34920652
Hematopoietic stem cell transplant for hyper-IgM syndrome due to CD40L defects: A single-center experience.
Al-Saud B, Al-Mousa H, Al-Ahmari A, Al-Ghonaium A, Ayas M, Alhissi S, Al-Muhsen S, Al-Seraihy A, Arnaout R, Al-Dhekri H, Hawwari A
Pediatr Transplant 2015 Sep;19(6):634-9. Epub 2015 Jun 13 doi: 10.1111/petr.12538. PMID: 26073206
Clinical features and hematopoietic stem cell transplantations for CD40 ligand deficiency in Japan.
Mitsui-Sekinaka K, Imai K, Sato H, Tomizawa D, Kajiwara M, Nagasawa M, Morio T, Nonoyama S
J Allergy Clin Immunol 2015 Oct;136(4):1018-24. Epub 2015 Mar 31 doi: 10.1016/j.jaci.2015.02.020. PMID: 25840720
Study of patients with Hyper-IgM type IV phenotype who recovered spontaneously during late childhood and review of the literature.
Karaca NE, Durandy A, Gulez N, Aksu G, Kutukculer N
Eur J Pediatr 2011 Aug;170(8):1039-47. Epub 2011 Jan 28 doi: 10.1007/s00431-011-1400-2. PMID: 21274562
Clinical and molecular characterization of X-linked hyper-IgM syndrome patients in China.
An Y, Xiao J, Jiang L, Yang X, Yu J, Zhao X
Scand J Immunol 2010 Jul;72(1):50-6. doi: 10.1111/j.1365-3083.2010.02406.x. PMID: 20591076

Diagnosis

Pulmonary Radiological Manifestations of Humoral and Combined Immunodeficiencies in a Tertiary Pediatric Center.
Khalili M, Farzi H, Darougar S, Hajijoo F, Mesdaghi M, Mansouri M, Babaie D, Hashemitari A, Eslami N, Chavoshzadeh Z
Iran J Allergy Asthma Immunol 2021 Dec 8;20(6):693-699. doi: 10.18502/ijaai.v20i6.8020. PMID: 34920652
A Hyper-IgM Syndrome Mutation in Activation-Induced Cytidine Deaminase Disrupts G-Quadruplex Binding and Genome-wide Chromatin Localization.
Yewdell WT, Kim Y, Chowdhury P, Lau CM, Smolkin RM, Belcheva KT, Fernandez KC, Cols M, Yen WF, Vaidyanathan B, Angeletti D, McDermott AB, Yewdell JW, Sun JC, Chaudhuri J
Immunity 2020 Nov 17;53(5):952-970.e11. Epub 2020 Oct 23 doi: 10.1016/j.immuni.2020.10.003. PMID: 33098766Free PMC Article
X-Linked Hyper IgM Syndrome Manifesting as Recurrent Pneumocystis jirovecii Pneumonia: A Case Report.
Huang SH, Meng XY, Bai ZJ, Li Y, Wu SY
J Trop Pediatr 2020 Dec 1;66(6):648-654. doi: 10.1093/tropej/fmaa023. PMID: 32388558
X-linked hyper IgM syndrome: clinical, immunological and molecular features in patients from India.
Madkaikar M, Gupta M, Chavan S, Italia K, Desai M, Merchant R, Radhakrishnan N, Ghosh K
Blood Cells Mol Dis 2014 Sep;53(3):99-104. Epub 2014 Jun 11 doi: 10.1016/j.bcmd.2014.05.008. PMID: 24929972
Hyper-IgM syndrome--a case report and a clinical perspective.
Silva R, Da Costa JT
Eur Ann Allergy Clin Immunol 2010 Oct;42(5):194-6. PMID: 21192628

Therapy

X-Linked Hyper IgM Syndrome Manifesting as Recurrent Pneumocystis jirovecii Pneumonia: A Case Report.
Huang SH, Meng XY, Bai ZJ, Li Y, Wu SY
J Trop Pediatr 2020 Dec 1;66(6):648-654. doi: 10.1093/tropej/fmaa023. PMID: 32388558
A Novel CD40L Mutation Associated with X-Linked Hyper IgM Syndrome in a Chinese Family.
Li L, Ji J, Han M, Xu Y, Zhang X, Liu W, Liu S
Immunol Invest 2020 Apr;49(3):307-316. Epub 2019 Aug 12 doi: 10.1080/08820139.2019.1638397. PMID: 31401902
CD40 ligand deficiency: treatment strategies and novel therapeutic perspectives.
França TT, Barreiros LA, Al-Ramadi BK, Ochs HD, Cabral-Marques O, Condino-Neto A
Expert Rev Clin Immunol 2019 May;15(5):529-540. Epub 2019 Feb 18 doi: 10.1080/1744666X.2019.1573674. PMID: 30681380
Clinical features and genetic analysis of 20 Chinese patients with X-linked hyper-IgM syndrome.
Wang LL, Zhou W, Zhao W, Tian ZQ, Wang WF, Wang XF, Chen TX
J Immunol Res 2014;2014:683160. Epub 2014 Aug 20 doi: 10.1155/2014/683160. PMID: 25215306Free PMC Article
Hyper-IgM syndrome--a case report and a clinical perspective.
Silva R, Da Costa JT
Eur Ann Allergy Clin Immunol 2010 Oct;42(5):194-6. PMID: 21192628

Prognosis

CD40 ligand deficiency: treatment strategies and novel therapeutic perspectives.
França TT, Barreiros LA, Al-Ramadi BK, Ochs HD, Cabral-Marques O, Condino-Neto A
Expert Rev Clin Immunol 2019 May;15(5):529-540. Epub 2019 Feb 18 doi: 10.1080/1744666X.2019.1573674. PMID: 30681380
Hematopoietic stem cell transplant for hyper-IgM syndrome due to CD40L defects: A single-center experience.
Al-Saud B, Al-Mousa H, Al-Ahmari A, Al-Ghonaium A, Ayas M, Alhissi S, Al-Muhsen S, Al-Seraihy A, Arnaout R, Al-Dhekri H, Hawwari A
Pediatr Transplant 2015 Sep;19(6):634-9. Epub 2015 Jun 13 doi: 10.1111/petr.12538. PMID: 26073206
X-linked hyper-IgM syndrome with CD40LG mutation: two case reports and literature review in Taiwanese patients.
Tsai HY, Yu HH, Chien YH, Chu KH, Lau YL, Lee JH, Wang LC, Chiang BL, Yang YH
J Microbiol Immunol Infect 2015 Feb;48(1):113-8. Epub 2012 Sep 24 doi: 10.1016/j.jmii.2012.07.004. PMID: 23010537
Study of patients with Hyper-IgM type IV phenotype who recovered spontaneously during late childhood and review of the literature.
Karaca NE, Durandy A, Gulez N, Aksu G, Kutukculer N
Eur J Pediatr 2011 Aug;170(8):1039-47. Epub 2011 Jan 28 doi: 10.1007/s00431-011-1400-2. PMID: 21274562
A family of ligands for the TNF receptor superfamily.
Cosman D
Stem Cells 1994 Sep;12(5):440-55. doi: 10.1002/stem.5530120501. PMID: 7528588

Clinical prediction guides

Clinical features and hematopoietic stem cell transplantations for CD40 ligand deficiency in Japan.
Mitsui-Sekinaka K, Imai K, Sato H, Tomizawa D, Kajiwara M, Nagasawa M, Morio T, Nonoyama S
J Allergy Clin Immunol 2015 Oct;136(4):1018-24. Epub 2015 Mar 31 doi: 10.1016/j.jaci.2015.02.020. PMID: 25840720
X-linked hyper-IgM syndrome with CD40LG mutation: two case reports and literature review in Taiwanese patients.
Tsai HY, Yu HH, Chien YH, Chu KH, Lau YL, Lee JH, Wang LC, Chiang BL, Yang YH
J Microbiol Immunol Infect 2015 Feb;48(1):113-8. Epub 2012 Sep 24 doi: 10.1016/j.jmii.2012.07.004. PMID: 23010537
Clinical features and genetic analysis of 20 Chinese patients with X-linked hyper-IgM syndrome.
Wang LL, Zhou W, Zhao W, Tian ZQ, Wang WF, Wang XF, Chen TX
J Immunol Res 2014;2014:683160. Epub 2014 Aug 20 doi: 10.1155/2014/683160. PMID: 25215306Free PMC Article
X-linked hyper IgM syndrome: clinical, immunological and molecular features in patients from India.
Madkaikar M, Gupta M, Chavan S, Italia K, Desai M, Merchant R, Radhakrishnan N, Ghosh K
Blood Cells Mol Dis 2014 Sep;53(3):99-104. Epub 2014 Jun 11 doi: 10.1016/j.bcmd.2014.05.008. PMID: 24929972
Study of patients with Hyper-IgM type IV phenotype who recovered spontaneously during late childhood and review of the literature.
Karaca NE, Durandy A, Gulez N, Aksu G, Kutukculer N
Eur J Pediatr 2011 Aug;170(8):1039-47. Epub 2011 Jan 28 doi: 10.1007/s00431-011-1400-2. PMID: 21274562

Recent systematic reviews

AA Amyloidosis Secondary to Primary Immune Deficiency: About 40 Cases Including 2 New French Cases and a Systematic Literature Review.
Delplanque M, Galicier L, Oziol E, Ducharme-Bénard S, Oksenhendler E, Buob D, Grateau G, Boutboul D, Georgin-Lavialle S
J Allergy Clin Immunol Pract 2021 Feb;9(2):745-752.e1. Epub 2020 Sep 30 doi: 10.1016/j.jaip.2020.09.023. PMID: 33007500

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    • ClinVar
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    • GTR
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      Clinical tests in GTR
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      Related Medical Subject Headings
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      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
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