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Severe combined immunodeficiency due to DCLRE1C deficiency(RS-SCID)

MedGen UID:
355454
Concept ID:
C1865370
Disease or Syndrome
Synonyms: RS-SCID; SCID, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-POSITIVE, WITH SENSITIVITY TO IONIZING RADIATION; Severe combined immunodeficiency with sensitivity to ionizing radiation
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): DCLRE1C (10p13)
 
Monarch Initiative: MONDO:0011225
OMIM®: 602450
Orphanet: ORPHA275

Definition

Severe combined immunodeficiency (SCID) due to DCLRE1C deficiency is a type of SCID (see this term) characterized by severe and recurrent infections, diarrhea, failure to thrive, and cell sensitivity to ionizing radiation. [from ORDO]

Clinical features

From HPO
Genital ulcers
MedGen UID:
57716
Concept ID:
C0151281
Disease or Syndrome
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.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
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.
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).
Eosinophilia
MedGen UID:
41824
Concept ID:
C0014457
Disease or Syndrome
Increased count of eosinophils in the blood.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Otitis media
MedGen UID:
45253
Concept ID:
C0029882
Disease or Syndrome
Inflammation or infection of the middle ear.
Pneumonia
MedGen UID:
10813
Concept ID:
C0032285
Disease or Syndrome
Inflammation of any part of the lung parenchyma.
Sepsis
MedGen UID:
48626
Concept ID:
C0036690
Disease or Syndrome
Systemic inflammatory response to infection.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Severe combined immunodeficiency disease
MedGen UID:
88328
Concept ID:
C0085110
Disease or Syndrome
A type of primary immune deficiency that is characterized by a more severe defect in both the T- and B-lymphocyte systems.
Increased circulating IgE concentration
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
Generalized lymphadenopathy
MedGen UID:
96909
Concept ID:
C0476486
Finding
A generalized form of lymphadenopathy.
Absent tonsils
MedGen UID:
154366
Concept ID:
C0576999
Finding
Lack of observable tonsillar tissue.
Aplasia of the thymus
MedGen UID:
146900
Concept ID:
C0685894
Congenital Abnormality
Absence of the thymus. This feature may be appreciated by the lack of a thymic shadow upon radiographic examination.
Panhypogammaglobulinemia
MedGen UID:
233072
Concept ID:
C1328587
Finding
A reduction in the circulating levels of all the major classes of immunoglobulin. is characterized by profound decreases in all classes of immunoglobulin with an absence of circulating B lymphocytes.
B lymphocytopenia
MedGen UID:
340780
Concept ID:
C1855067
Finding
An abnormal decrease from the normal count of B cells.
Lymph node hypoplasia
MedGen UID:
892318
Concept ID:
C4025683
Finding
Underdevelopment of the lymph nodes.
Abnormally low T cell receptor excision circle level
MedGen UID:
1611921
Concept ID:
C4531052
Finding
Reduced level of T cell receptor excision circle (TRECs) as measured by the TREC assay. Late in maturation, 70% of thymocytes that will ultimately express alpha/beta-T cell receptors form a circular DNA TREC from the excised TCRdelta gene that lies within the TCRalpha genetic locus. The circles are stable but do not increase following cell division and, therefore, become diluted as T cells proliferate. A quantitative polymerase chain reaction (PCR) reaction across the joint of the circular DNA provides the TREC copy number, a marker of newly-formed, antigenically-naïve thymic emigrant T cells.
BCGitis
MedGen UID:
1684722
Concept ID:
C5139070
Disease or Syndrome
Local or regional infection with Bacillus Calmette-Guerin (BCG) following vaccination.
Oral ulcer
MedGen UID:
57699
Concept ID:
C0149745
Disease or Syndrome
Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue.
Alopecia of scalp
MedGen UID:
658454
Concept ID:
C0574769
Finding
Erythematous papule
MedGen UID:
834002
Concept ID:
C0747241
Finding
A circumscribed, solid elevation of skin with no visible fluid that is reddish (erythematous) in color.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSevere combined immunodeficiency due to DCLRE1C deficiency
Follow this link to review classifications for Severe combined immunodeficiency due to DCLRE1C deficiency in Orphanet.

Professional guidelines

PubMed

Boyarchuk O, Yarema N, Kravets V, Shulhai O, Shymanska I, Chornomydz I, Hariyan T, Volianska L, Kinash M, Makukh H
Front Immunol 2022;13:999664. Epub 2022 Sep 15 doi: 10.3389/fimmu.2022.999664. PMID: 36189201Free PMC Article
Haddad E, Logan BR, Griffith LM, Buckley RH, Parrott RE, Prockop SE, Small TN, Chaisson J, Dvorak CC, Murnane M, Kapoor N, Abdel-Azim H, Hanson IC, Martinez C, Bleesing JJH, Chandra S, Smith AR, Cavanaugh ME, Jyonouchi S, Sullivan KE, Burroughs L, Skoda-Smith S, Haight AE, Tumlin AG, Quigg TC, Taylor C, Dávila Saldaña BJ, Keller MD, Seroogy CM, Desantes KB, Petrovic A, Leiding JW, Shyr DC, Decaluwe H, Teira P, Gillio AP, Knutsen AP, Moore TB, Kletzel M, Craddock JA, Aquino V, Davis JH, Yu LC, Cuvelier GDE, Bednarski JJ, Goldman FD, Kang EM, Shereck E, Porteus MH, Connelly JA, Fleisher TA, Malech HL, Shearer WT, Szabolcs P, Thakar MS, Vander Lugt MT, Heimall J, Yin Z, Pulsipher MA, Pai SY, Kohn DB, Puck JM, Cowan MJ, O'Reilly RJ, Notarangelo LD
Blood 2018 Oct 25;132(17):1737-1749. Epub 2018 Aug 28 doi: 10.1182/blood-2018-03-840702. PMID: 30154114Free PMC Article

Recent clinical studies

Etiology

Hazar E, Karaselek MA, Kapakli H, Dogar O, Kuccukturk S, Uygun V, Artac H, Fındık S, Sahin A, Arslan S, Guner S, Reisli I, Keles S
Pediatr Allergy Immunol 2024 Oct;35(10):e14260. doi: 10.1111/pai.14260. PMID: 39425552
Dvorak CC, Haddad E, Heimall J, Dunn E, Cowan MJ, Pai SY, Kapoor N, Satter LF, Buckley RH, O'Reilly RJ, Chandra S, Bednarski JJ, Williams O, Rayes A, Moore TB, Ebens CL, Davila Saldana BJ, Petrovic A, Chellapandian D, Cuvelier GDE, Vander Lugt MT, Caywood EH, Chandrakasan S, Eissa H, Goldman FD, Shereck E, Aquino VM, Desantes KB, Madden LM, Miller HK, Yu L, Broglie L, Gillio A, Shah AJ, Knutsen AP, Andolina JP, Joshi AY, Szabolcs P, Kapadia M, Martinez CA, Parrot RE, Sullivan KE, Prockop SE, Abraham RS, Thakar MS, Leiding JW, Kohn DB, Pulsipher MA, Griffith LM, Notarangelo LD, Puck JM
J Allergy Clin Immunol 2023 Feb;151(2):547-555.e5. Epub 2022 Nov 28 doi: 10.1016/j.jaci.2022.10.021. PMID: 36456360Free PMC Article
Boyarchuk O, Yarema N, Kravets V, Shulhai O, Shymanska I, Chornomydz I, Hariyan T, Volianska L, Kinash M, Makukh H
Front Immunol 2022;13:999664. Epub 2022 Sep 15 doi: 10.3389/fimmu.2022.999664. PMID: 36189201Free PMC Article
Aykut A, Durmaz A, Karaca N, Gulez N, Genel F, Celmeli F, Ozturk G, Atay D, Aydogmus C, Kiykim A, Aksu G, Kutukculer N
Scand J Immunol 2022 Jun;95(6):e13163. Epub 2022 Mar 23 doi: 10.1111/sji.13163. PMID: 35303369
Kalina T, Bakardjieva M, Blom M, Perez-Andres M, Barendregt B, Kanderová V, Bonroy C, Philippé J, Blanco E, Pico-Knijnenburg I, Paping JHMP, Wolska-Kuśnierz B, Pac M, Tkazcyk J, Haerynck F, Akar HH, Formánková R, Freiberger T, Svatoň M, Šedivá A, Arriba-Méndez S, Orfao A, van Dongen JJM, van der Burg M
Front Immunol 2020;11:371. Epub 2020 Mar 19 doi: 10.3389/fimmu.2020.00371. PMID: 32265901Free PMC Article

Diagnosis

Hazar E, Karaselek MA, Kapakli H, Dogar O, Kuccukturk S, Uygun V, Artac H, Fındık S, Sahin A, Arslan S, Guner S, Reisli I, Keles S
Pediatr Allergy Immunol 2024 Oct;35(10):e14260. doi: 10.1111/pai.14260. PMID: 39425552
Dvorak CC, Haddad E, Heimall J, Dunn E, Cowan MJ, Pai SY, Kapoor N, Satter LF, Buckley RH, O'Reilly RJ, Chandra S, Bednarski JJ, Williams O, Rayes A, Moore TB, Ebens CL, Davila Saldana BJ, Petrovic A, Chellapandian D, Cuvelier GDE, Vander Lugt MT, Caywood EH, Chandrakasan S, Eissa H, Goldman FD, Shereck E, Aquino VM, Desantes KB, Madden LM, Miller HK, Yu L, Broglie L, Gillio A, Shah AJ, Knutsen AP, Andolina JP, Joshi AY, Szabolcs P, Kapadia M, Martinez CA, Parrot RE, Sullivan KE, Prockop SE, Abraham RS, Thakar MS, Leiding JW, Kohn DB, Pulsipher MA, Griffith LM, Notarangelo LD, Puck JM
J Allergy Clin Immunol 2023 Feb;151(2):547-555.e5. Epub 2022 Nov 28 doi: 10.1016/j.jaci.2022.10.021. PMID: 36456360Free PMC Article
Inoue K, Miyamoto S, Tomomasa D, Adachi E, Azumi S, Horikoshi Y, Ishihara T, Osone S, Kawahara Y, Kudo K, Kato Z, Ohnishi H, Kashimada K, Imai K, Ohara O, van Zelm MC, Cowan MJ, Morio T, Kanegane H
J Clin Immunol 2023 Apr;43(3):585-594. Epub 2022 Nov 16 doi: 10.1007/s10875-022-01405-3. PMID: 36385359
Cowan MJ, Yu J, Facchino J, Fraser-Browne C, Sanford U, Kawahara M, Dara J, Long-Boyle J, Oh J, Chan W, Chag S, Broderick L, Chellapandian D, Decaluwe H, Golski C, Hu D, Kuo CY, Miller HK, Petrovic A, Currier R, Hilton JF, Punwani D, Dvorak CC, Malech HL, McIvor RS, Puck JM
N Engl J Med 2022 Dec 22;387(25):2344-2355. doi: 10.1056/NEJMoa2206575. PMID: 36546626Free PMC Article
Al-Herz W, Massaad MJ, Chou J, Notarangelo LD, Geha RS
Clin Immunol 2018 Feb;187:68-75. Epub 2017 Oct 16 doi: 10.1016/j.clim.2017.10.006. PMID: 29051008Free PMC Article

Therapy

Cowan MJ, Yu J, Facchino J, Fraser-Browne C, Sanford U, Kawahara M, Dara J, Long-Boyle J, Oh J, Chan W, Chag S, Broderick L, Chellapandian D, Decaluwe H, Golski C, Hu D, Kuo CY, Miller HK, Petrovic A, Currier R, Hilton JF, Punwani D, Dvorak CC, Malech HL, McIvor RS, Puck JM
N Engl J Med 2022 Dec 22;387(25):2344-2355. doi: 10.1056/NEJMoa2206575. PMID: 36546626Free PMC Article
Al-Herz W, Massaad MJ, Chou J, Notarangelo LD, Geha RS
Clin Immunol 2018 Feb;187:68-75. Epub 2017 Oct 16 doi: 10.1016/j.clim.2017.10.006. PMID: 29051008Free PMC Article
Punwani D, Kawahara M, Yu J, Sanford U, Roy S, Patel K, Carbonaro DA, Karlen AD, Khan S, Cornetta K, Rothe M, Schambach A, Kohn DB, Malech HL, McIvor RS, Puck JM, Cowan MJ
Hum Gene Ther 2017 Jan;28(1):112-124. Epub 2016 Sep 7 doi: 10.1089/hum.2016.064. PMID: 27611239Free PMC Article
Rivera-Munoz P, Abramowski V, Jacquot S, André P, Charrier S, Lipson-Ruffert K, Fischer A, Galy A, Cavazzana M, de Villartay JP
Gene Ther 2016 Feb;23(2):176-86. Epub 2015 Oct 1 doi: 10.1038/gt.2015.95. PMID: 26361272
Mostoslavsky G, Fabian AJ, Rooney S, Alt FW, Mulligan RC
Proc Natl Acad Sci U S A 2006 Oct 31;103(44):16406-11. Epub 2006 Oct 24 doi: 10.1073/pnas.0608130103. PMID: 17062750Free PMC Article

Prognosis

Hazar E, Karaselek MA, Kapakli H, Dogar O, Kuccukturk S, Uygun V, Artac H, Fındık S, Sahin A, Arslan S, Guner S, Reisli I, Keles S
Pediatr Allergy Immunol 2024 Oct;35(10):e14260. doi: 10.1111/pai.14260. PMID: 39425552
Aykut A, Durmaz A, Karaca N, Gulez N, Genel F, Celmeli F, Ozturk G, Atay D, Aydogmus C, Kiykim A, Aksu G, Kutukculer N
Scand J Immunol 2022 Jun;95(6):e13163. Epub 2022 Mar 23 doi: 10.1111/sji.13163. PMID: 35303369
Strubbe S, De Bruyne M, Pannicke U, Beyls E, Vandekerckhove B, Leclercq G, De Baere E, Bordon V, Vral A, Schwarz K, Haerynck F, Taghon T
Front Immunol 2021;12:674226. Epub 2021 Jun 17 doi: 10.3389/fimmu.2021.674226. PMID: 34220820Free PMC Article
Haddad E, Logan BR, Griffith LM, Buckley RH, Parrott RE, Prockop SE, Small TN, Chaisson J, Dvorak CC, Murnane M, Kapoor N, Abdel-Azim H, Hanson IC, Martinez C, Bleesing JJH, Chandra S, Smith AR, Cavanaugh ME, Jyonouchi S, Sullivan KE, Burroughs L, Skoda-Smith S, Haight AE, Tumlin AG, Quigg TC, Taylor C, Dávila Saldaña BJ, Keller MD, Seroogy CM, Desantes KB, Petrovic A, Leiding JW, Shyr DC, Decaluwe H, Teira P, Gillio AP, Knutsen AP, Moore TB, Kletzel M, Craddock JA, Aquino V, Davis JH, Yu LC, Cuvelier GDE, Bednarski JJ, Goldman FD, Kang EM, Shereck E, Porteus MH, Connelly JA, Fleisher TA, Malech HL, Shearer WT, Szabolcs P, Thakar MS, Vander Lugt MT, Heimall J, Yin Z, Pulsipher MA, Pai SY, Kohn DB, Puck JM, Cowan MJ, O'Reilly RJ, Notarangelo LD
Blood 2018 Oct 25;132(17):1737-1749. Epub 2018 Aug 28 doi: 10.1182/blood-2018-03-840702. PMID: 30154114Free PMC Article
Lee PP, Woodbine L, Gilmour KC, Bibi S, Cale CM, Amrolia PJ, Veys PA, Davies EG, Jeggo PA, Jones A
Clin Immunol 2013 Dec;149(3):464-74. Epub 2013 Aug 27 doi: 10.1016/j.clim.2013.08.006. PMID: 24230999

Clinical prediction guides

Hazar E, Karaselek MA, Kapakli H, Dogar O, Kuccukturk S, Uygun V, Artac H, Fındık S, Sahin A, Arslan S, Guner S, Reisli I, Keles S
Pediatr Allergy Immunol 2024 Oct;35(10):e14260. doi: 10.1111/pai.14260. PMID: 39425552
Strubbe S, De Bruyne M, Pannicke U, Beyls E, Vandekerckhove B, Leclercq G, De Baere E, Bordon V, Vral A, Schwarz K, Haerynck F, Taghon T
Front Immunol 2021;12:674226. Epub 2021 Jun 17 doi: 10.3389/fimmu.2021.674226. PMID: 34220820Free PMC Article
Volk T, Pannicke U, Reisli I, Bulashevska A, Ritter J, Björkman A, Schäffer AA, Fliegauf M, Sayar EH, Salzer U, Fisch P, Pfeifer D, Di Virgilio M, Cao H, Yang F, Zimmermann K, Keles S, Caliskaner Z, Güner SÜ, Schindler D, Hammarström L, Rizzi M, Hummel M, Pan-Hammarström Q, Schwarz K, Grimbacher B
Hum Mol Genet 2015 Dec 20;24(25):7361-72. Epub 2015 Oct 16 doi: 10.1093/hmg/ddv437. PMID: 26476407Free PMC Article
Felgentreff K, Lee YN, Frugoni F, Du L, van der Burg M, Giliani S, Tezcan I, Reisli I, Mejstrikova E, de Villartay JP, Sleckman BP, Manis J, Notarangelo LD
J Allergy Clin Immunol 2015 Jul;136(1):140-150.e7. Epub 2015 Apr 25 doi: 10.1016/j.jaci.2015.03.005. PMID: 25917813Free PMC Article
Lee PP, Woodbine L, Gilmour KC, Bibi S, Cale CM, Amrolia PJ, Veys PA, Davies EG, Jeggo PA, Jones A
Clin Immunol 2013 Dec;149(3):464-74. Epub 2013 Aug 27 doi: 10.1016/j.clim.2013.08.006. PMID: 24230999

Recent systematic reviews

Lee PP, Woodbine L, Gilmour KC, Bibi S, Cale CM, Amrolia PJ, Veys PA, Davies EG, Jeggo PA, Jones A
Clin Immunol 2013 Dec;149(3):464-74. Epub 2013 Aug 27 doi: 10.1016/j.clim.2013.08.006. PMID: 24230999

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