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TFRC-related combined immunodeficiency(IMD46)

MedGen UID:
1799556
•Concept ID:
C5568133
•
Disease or Syndrome
Synonym: Immunodeficiency 46
SNOMED CT: Combined immunodeficiency due to transferrin receptor deficiency (1179288008); TFRC (transferrin receptor) related combined immunodeficiency (1179288008); Combined immunodeficiency due to TFRC deficiency (1179288008)
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).
Autosomal recessive inheritance (Orphanet)
 
Gene (location): TFRC (3q29)
 
Monarch Initiative: MONDO:0014760
OMIM®: 616740
Orphanet: ORPHA476113

Definition

A rare genetic combined T and B cell immunodeficiency characterised by life-threatening infections due to disrupted transferrin receptor 1 endocytosis, resulting in defective cellular iron transport and impaired T and B cell function. Patients present with early-onset chronic diarrhoea, severe recurrent infections and failure to thrive. Laboratory studies reveal hypo or agammaglobulinaemia, normal lymphocyte counts but decreased numbers of memory B cells, intermittent neutropenia and thrombocytopenia, and mild anaemia (resistant to iron supplementation) with low mean corpuscular volume. [from SNOMEDCT_US]

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
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.
See: Feature record | Search on this feature
Anemia
MedGen UID:
1526
•Concept ID:
C0002871
•
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
See: Feature record | Search on this feature
Intermittent thrombocytopenia
MedGen UID:
374151
•Concept ID:
C1839167
•
Finding
Reduced platelet count that occurs sporadically, i.e., it comes and goes.
See: Feature record | Search on this feature
Recurrent sinopulmonary infections
MedGen UID:
339549
•Concept ID:
C1846546
•
Finding
An increased susceptibility to infections involving both the paranasal sinuses and the lungs, as manifested by a history of recurrent sinopulmonary infections.
See: Feature record | Search on this feature
Conjunctivitis
MedGen UID:
1093
•Concept ID:
C0009763
•
Disease or Syndrome
Inflammation of the conjunctiva.
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
Meningitis
MedGen UID:
6298
•Concept ID:
C0025289
•
Disease or Syndrome
Inflammation of the meninges.
See: Feature record | Search on this feature
Sepsis
MedGen UID:
48626
•Concept ID:
C0036690
•
Disease or Syndrome
Systemic inflammatory response to infection.
See: Feature record | Search on this feature
Neutropenia
MedGen UID:
163121
•Concept ID:
C0853697
•
Finding
An abnormally low number of neutrophils in the peripheral blood.
See: Feature record | Search on this feature
Chronic oral candidiasis
MedGen UID:
870166
•Concept ID:
C4024599
•
Disease or Syndrome
Chronic accumulation and overgrowth of the fungus Candida albicans on the mucous membranes of the mouth, generally manifested as associated with creamy white lesions on the tongue or inner cheeks, occasionally spreading to the gums, tonsils, palate or oropharynx.
See: Feature record | Search on this feature
Decreased circulating antibody concentration
MedGen UID:
892481
•Concept ID:
C4048270
•
Finding
An abnormally decreased level of immunoglobulin in blood.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVTFRC-related combined immunodeficiency

Professional guidelines

PubMed

The diagnosis of severe combined immunodeficiency (SCID): The Primary Immune Deficiency Treatment Consortium (PIDTC) 2022 Definitions.
Dvorak CC, Haddad E, Heimall J, Dunn E, Buckley RH, Kohn DB, Cowan MJ, Pai SY, Griffith LM, Cuvelier GDE, Eissa H, Shah AJ, O'Reilly RJ, Pulsipher MA, Wright NAM, Abraham RS, Satter LF, Notarangelo LD, Puck JM
J Allergy Clin Immunol 2023 Feb;151(2):539-546. Epub 2022 Nov 28 doi: 10.1016/j.jaci.2022.10.022. PMID: 36456361Free PMC Article
Diagnosis and treatment of Merkel cell carcinoma: European consensus-based interdisciplinary guideline - Update 2022.
Gauci ML, Aristei C, Becker JC, Blom A, Bataille V, Dreno B, Del Marmol V, Forsea AM, Fargnoli MC, Grob JJ, Gomes F, Hauschild A, Hoeller C, Harwood C, Kelleners-Smeets N, Kaufmann R, Lallas A, Malvehy J, Moreno-Ramirez D, Peris K, Pellacani G, Saiag P, Stratigos AJ, Vieira R, Zalaudek I, van Akkooi ACJ, Lorigan P, Garbe C, Lebbé C; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC)
Eur J Cancer 2022 Aug;171:203-231. Epub 2022 Jun 19 doi: 10.1016/j.ejca.2022.03.043. PMID: 35732101
Position statement: LEPROSY: Diagnosis, treatment and follow-up.
Alemu Belachew W, Naafs B
J Eur Acad Dermatol Venereol 2019 Jul;33(7):1205-1213. Epub 2019 Apr 3 doi: 10.1111/jdv.15569. PMID: 30945360

Recent clinical studies

Etiology

Primary and secondary defects of the thymus.
Dinges SS, Amini K, Notarangelo LD, Delmonte OM
Immunol Rev 2024 Mar;322(1):178-211. Epub 2024 Jan 16 doi: 10.1111/imr.13306. PMID: 38228406Free PMC Article
Monogenic Adult-Onset Inborn Errors of Immunity.
Staels F, Collignon T, Betrains A, Gerbaux M, Willemsen M, Humblet-Baron S, Liston A, Vanderschueren S, Schrijvers R
Front Immunol 2021;12:753978. Epub 2021 Nov 17 doi: 10.3389/fimmu.2021.753978. PMID: 34867986Free PMC Article
Combined immunodeficiencies.
Aranda CS, Guimarães RR, de Gouveia-Pereira Pimentel M
J Pediatr (Rio J) 2021 Mar-Apr;97 Suppl 1(Suppl 1):S39-S48. Epub 2020 Dec 17 doi: 10.1016/j.jped.2020.10.014. PMID: 33340461Free PMC Article
Flow cytometry-based diagnosis of primary immunodeficiency diseases.
Kanegane H, Hoshino A, Okano T, Yasumi T, Wada T, Takada H, Okada S, Yamashita M, Yeh TW, Nishikomori R, Takagi M, Imai K, Ochs HD, Morio T
Allergol Int 2018 Jan;67(1):43-54. Epub 2017 Jul 3 doi: 10.1016/j.alit.2017.06.003. PMID: 28684198
Genetic immunodeficiency diseases.
Abrams M, Paller A
Adv Dermatol 2007;23:197-229. doi: 10.1016/j.yadr.2007.08.001. PMID: 18159903

Diagnosis

Good's syndrome: brief overview of an enigmatic immune deficiency.
Sipos F, Műzes G
APMIS 2023 Dec;131(12):698-704. Epub 2023 Sep 20 doi: 10.1111/apm.13351. PMID: 37729389
The diagnosis of severe combined immunodeficiency (SCID): The Primary Immune Deficiency Treatment Consortium (PIDTC) 2022 Definitions.
Dvorak CC, Haddad E, Heimall J, Dunn E, Buckley RH, Kohn DB, Cowan MJ, Pai SY, Griffith LM, Cuvelier GDE, Eissa H, Shah AJ, O'Reilly RJ, Pulsipher MA, Wright NAM, Abraham RS, Satter LF, Notarangelo LD, Puck JM
J Allergy Clin Immunol 2023 Feb;151(2):539-546. Epub 2022 Nov 28 doi: 10.1016/j.jaci.2022.10.022. PMID: 36456361Free PMC Article
Monogenic Adult-Onset Inborn Errors of Immunity.
Staels F, Collignon T, Betrains A, Gerbaux M, Willemsen M, Humblet-Baron S, Liston A, Vanderschueren S, Schrijvers R
Front Immunol 2021;12:753978. Epub 2021 Nov 17 doi: 10.3389/fimmu.2021.753978. PMID: 34867986Free PMC Article
Approach to primary immunodeficiency.
Devonshire AL, Makhija M
Allergy Asthma Proc 2019 Nov 1;40(6):465-469. doi: 10.2500/aap.2019.40.4273. PMID: 31690396Free PMC Article
Flow cytometry-based diagnosis of primary immunodeficiency diseases.
Kanegane H, Hoshino A, Okano T, Yasumi T, Wada T, Takada H, Okada S, Yamashita M, Yeh TW, Nishikomori R, Takagi M, Imai K, Ochs HD, Morio T
Allergol Int 2018 Jan;67(1):43-54. Epub 2017 Jul 3 doi: 10.1016/j.alit.2017.06.003. PMID: 28684198

Therapy

Clinical and functional spectrum of RAC2-related immunodeficiency.
Donkó Á, Sharapova SO, Kabat J, Ganesan S, Hauck FH, Bergerson JRE, Marois L, Abbott J, Moshous D, Williams KW, Campbell N, Martin PL, Lagresle-Peyrou C, Trojan T, Kuzmenko NB, Deordieva EA, Raykina EV, Abers MS, Abolhassani H, Barlogis V, Milla C, Hall G, Mousallem T, Church J, Kapoor N, Cros G, Chapdelaine H, Franco-Jarava C, Lopez-Lerma I, Miano M, Leiding JW, Klein C, Stasia MJ, Fischer A, Hsiao KC, Martelius T, Seppänen MRJ, Barmettler S, Walter J, Masmas TN, Mukhina AA, Falcone EL, Kracker S, Shcherbina A, Holland SM, Leto TL, Hsu AP
Blood 2024 Apr 11;143(15):1476-1487. doi: 10.1182/blood.2023022098. PMID: 38194689Free PMC Article
Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities.
Bittner B, Richter W, Schmidt J
BioDrugs 2018 Oct;32(5):425-440. doi: 10.1007/s40259-018-0295-0. PMID: 30043229Free PMC Article
Gene Therapy Approaches to Immunodeficiency.
Ghosh S, Gaspar HB
Hematol Oncol Clin North Am 2017 Oct;31(5):823-834. Epub 2017 Jun 29 doi: 10.1016/j.hoc.2017.05.003. PMID: 28895850
Primary immunodeficiencies.
Notarangelo LD
J Allergy Clin Immunol 2010 Feb;125(2 Suppl 2):S182-94. Epub 2009 Dec 29 doi: 10.1016/j.jaci.2009.07.053. PMID: 20042228
Primary immunodeficiencies.
Cooper MA, Pommering TL, Korányi K
Am Fam Physician 2003 Nov 15;68(10):2001-8. PMID: 14655810

Prognosis

Editorial: Advances in Primary Immunodeficiency in Central-Eastern Europe.
Pac M, Casanova JL, Reisli I, Maródi L
Front Immunol 2021;12:667727. Epub 2021 May 14 doi: 10.3389/fimmu.2021.667727. PMID: 34084169Free PMC Article
Combined immunodeficiencies.
Aranda CS, Guimarães RR, de Gouveia-Pereira Pimentel M
J Pediatr (Rio J) 2021 Mar-Apr;97 Suppl 1(Suppl 1):S39-S48. Epub 2020 Dec 17 doi: 10.1016/j.jped.2020.10.014. PMID: 33340461Free PMC Article
Tuberculous meningitis.
Garg RK
Acta Neurol Scand 2010 Aug;122(2):75-90. Epub 2010 Jan 6 doi: 10.1111/j.1600-0404.2009.01316.x. PMID: 20055767
Primary immunodeficiencies.
Cooper MA, Pommering TL, Korányi K
Am Fam Physician 2003 Nov 15;68(10):2001-8. PMID: 14655810
Non-Hodgkin's lymphomas.
Haller DG
Med Clin North Am 1984 May;68(3):741-56. doi: 10.1016/s0025-7125(16)31126-9. PMID: 6205233

Clinical prediction guides

Clinical and functional spectrum of RAC2-related immunodeficiency.
Donkó Á, Sharapova SO, Kabat J, Ganesan S, Hauck FH, Bergerson JRE, Marois L, Abbott J, Moshous D, Williams KW, Campbell N, Martin PL, Lagresle-Peyrou C, Trojan T, Kuzmenko NB, Deordieva EA, Raykina EV, Abers MS, Abolhassani H, Barlogis V, Milla C, Hall G, Mousallem T, Church J, Kapoor N, Cros G, Chapdelaine H, Franco-Jarava C, Lopez-Lerma I, Miano M, Leiding JW, Klein C, Stasia MJ, Fischer A, Hsiao KC, Martelius T, Seppänen MRJ, Barmettler S, Walter J, Masmas TN, Mukhina AA, Falcone EL, Kracker S, Shcherbina A, Holland SM, Leto TL, Hsu AP
Blood 2024 Apr 11;143(15):1476-1487. doi: 10.1182/blood.2023022098. PMID: 38194689Free PMC Article
Gene therapy for severe combined immunodeficiencies and beyond.
Fischer A, Hacein-Bey-Abina S
J Exp Med 2020 Jan 6;217(2) doi: 10.1084/jem.20190607. PMID: 31826240Free PMC Article
Defining combined immunodeficiency.
Roifman CM, Somech R, Kavadas F, Pires L, Nahum A, Dalal I, Grunebaum E
J Allergy Clin Immunol 2012 Jul;130(1):177-83. Epub 2012 Jun 2 doi: 10.1016/j.jaci.2012.04.029. PMID: 22664165
DOCK8 deficiency.
Su HC, Jing H, Zhang Q
Ann N Y Acad Sci 2011 Dec;1246:26-33. doi: 10.1111/j.1749-6632.2011.06295.x. PMID: 22236427
Graft-vs-host reaction.
Grogan TM, Odom RB, Burgess JH
Arch Dermatol 1977 Jun;113(6):806-12. PMID: 17368

Recent systematic reviews

Oral pre-exposure prophylaxis (PrEP) to prevent HIV: a systematic review and meta-analysis of clinical effectiveness, safety, adherence and risk compensation in all populations.
O Murchu E, Marshall L, Teljeur C, Harrington P, Hayes C, Moran P, Ryan M
BMJ Open 2022 May 11;12(5):e048478. doi: 10.1136/bmjopen-2020-048478. PMID: 35545381Free PMC Article
Non-invasive diagnosis of Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis.
Senécal J, Smyth E, Del Corpo O, Hsu JM, Amar-Zifkin A, Bergeron A, Cheng MP, Butler-Laporte G, McDonald EG, Lee TC
Clin Microbiol Infect 2022 Jan;28(1):23-30. Epub 2021 Aug 28 doi: 10.1016/j.cmi.2021.08.017. PMID: 34464734
Estimates of the global burden of cervical cancer associated with HIV.
Stelzle D, Tanaka LF, Lee KK, Ibrahim Khalil A, Baussano I, Shah ASV, McAllister DA, Gottlieb SL, Klug SJ, Winkler AS, Bray F, Baggaley R, Clifford GM, Broutet N, Dalal S
Lancet Glob Health 2021 Feb;9(2):e161-e169. Epub 2020 Nov 16 doi: 10.1016/S2214-109X(20)30459-9. PMID: 33212031Free PMC Article
Idiopathic multicentric Castleman's disease: a systematic literature review.
Liu AY, Nabel CS, Finkelman BS, Ruth JR, Kurzrock R, van Rhee F, Krymskaya VP, Kelleher D, Rubenstein AH, Fajgenbaum DC
Lancet Haematol 2016 Apr;3(4):e163-75. Epub 2016 Mar 17 doi: 10.1016/S2352-3026(16)00006-5. PMID: 27063975
Estimating per-act HIV transmission risk: a systematic review.
Patel P, Borkowf CB, Brooks JT, Lasry A, Lansky A, Mermin J
AIDS 2014 Jun 19;28(10):1509-19. doi: 10.1097/QAD.0000000000000298. PMID: 24809629Free PMC Article

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      Clinical tests in GTR
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