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T-B+ severe combined immunodeficiency due to JAK3 deficiency

MedGen UID:
331474
Concept ID:
C1833275
Disease or Syndrome
Synonyms: SCID, autosomal recessive, T-negative/B-positive type; SCID, T CELL-NEGATIVE, B CELL-POSITIVE, NK CELL-NEGATIVE; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-negative
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): JAK3 (19p13.11)
 
Monarch Initiative: MONDO:0010938
OMIM®: 600802
Orphanet: ORPHA35078

Definition

JAK3-deficient severe combined immunodeficiency (SCID) is an inherited disorder of the immune system. Individuals with JAK3-deficient SCID lack the necessary immune cells to fight off certain bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. Often the organisms that cause infection in people with JAK3-deficient SCID are described as opportunistic because they ordinarily do not cause illness in healthy people. Affected infants typically develop chronic diarrhea, a fungal infection in the mouth called oral thrush, pneumonia, and skin rashes. Persistent illness also causes affected individuals to grow more slowly than other children. Without treatment, people with JAK3-deficient SCID usually live only into early childhood. [from MedlinePlus Genetics]

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.
Intestinal obstruction
MedGen UID:
43933
Concept ID:
C0021843
Disease or Syndrome
Blockage or impairment of the normal flow of the contents of the intestine towards the anal canal.
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).
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.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Meningitis
MedGen UID:
6298
Concept ID:
C0025289
Disease or Syndrome
Inflammation of the meninges.
Pneumonia
MedGen UID:
10813
Concept ID:
C0032285
Disease or Syndrome
Inflammation of any part of the lung parenchyma.
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.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
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.
Abnormality of B cell physiology
MedGen UID:
341411
Concept ID:
C1849242
Finding
An abnormality of the physiological functioning of B cells.
Cutaneous anergy
MedGen UID:
344575
Concept ID:
C1855781
Finding
Inability to react to a delayed hypersensitivity skin test.
T lymphocytopenia
MedGen UID:
419385
Concept ID:
C2931322
Finding
An abnormally low count of T cells.
Impaired lymphocyte transformation with phytohemagglutinin
MedGen UID:
871152
Concept ID:
C4025625
Finding
Normal peripheral blood lymphocytes, when stimulated by phytohemagglutinin (PHA) are cytotoxic for homologous and heterologous cells but not for autologous cells in monolayer culture. The cytotoxic effect is thought to be indicative of the immunological competence of the lymphocytes.
Absent natural killer cells
MedGen UID:
892985
Concept ID:
C4073163
Finding
Lack of natural killer cells, a type of lymphocyte in the innate immune system that contains cytoplasmic granzymes, i.e., small granules with perforin and proteases that allow natural killer cells to form pores in the cell membrane of the target cell through which the granzymes and associated molecules can enter, inducing apoptosis.
Decreased lymphocyte proliferation in response to anti-CD3
MedGen UID:
1614554
Concept ID:
C4531165
Finding
A decreased proliferative response of lymphocytes in vitro or in vivo, when stimulated with an anti-CD3 antibody against the T-cell co-receptor, CD3.
Absent peripheral lymph nodes in presence of infection
MedGen UID:
1780141
Concept ID:
C5539700
Finding
The absence of any palpable lymph nodes in the presence of symptoms suggesting infection in that drainage area should raise suspicion for immunodeficiency diseases.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVT-B+ severe combined immunodeficiency due to JAK3 deficiency
Follow this link to review classifications for T-B+ severe combined immunodeficiency due to JAK3 deficiency in Orphanet.

Professional guidelines

PubMed

Schumacher RF, Mella P, Lalatta F, Fiorini M, Giliani S, Villa A, Candotti F, Notarangelo LD
Prenat Diagn 1999 Jul;19(7):653-6. PMID: 10419614

Recent clinical studies

Etiology

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
Aluri J, Desai M, Gupta M, Dalvi A, Terance A, Rosenzweig SD, Stoddard JL, Niemela JE, Tamankar V, Mhatre S, Bargir U, Kulkarni M, Shah N, Aggarwal A, Lashkari HP, Krishna V, Govindaraj G, Kalra M, Madkaikar M
Front Immunol 2019;10:23. Epub 2019 Feb 4 doi: 10.3389/fimmu.2019.00023. PMID: 30778343Free PMC Article
Stepensky P, Keller B, Shamriz O, NaserEddin A, Rumman N, Weintraub M, Warnatz K, Elpeleg O, Barak Y
Clin Immunol 2016 Feb;163:91-5. Epub 2016 Jan 6 doi: 10.1016/j.clim.2016.01.001. PMID: 26769277
Buckley RH, Win CM, Moser BK, Parrott RE, Sajaroff E, Sarzotti-Kelsoe M
J Clin Immunol 2013 Jan;33(1):96-110. Epub 2012 Sep 22 doi: 10.1007/s10875-012-9797-6. PMID: 23001410Free PMC Article
Michos A, Tzanoudaki M, Villa A, Giliani S, Chrousos G, Kanariou M
J Clin Immunol 2011 Oct;31(5):778-83. Epub 2011 Jul 6 doi: 10.1007/s10875-011-9564-0. PMID: 21732012

Diagnosis

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
El Hawary R, Meshaal S, Mauracher AA, Opitz L, Abd Elaziz D, Lotfy S, Eldash A, Boutros J, Galal N, Pachlopnik Schmid J, Elmarsafy A
Clin Exp Immunol 2021 Mar;203(3):448-457. Epub 2020 Nov 2 doi: 10.1111/cei.13536. PMID: 33040328Free PMC Article
Aluri J, Desai M, Gupta M, Dalvi A, Terance A, Rosenzweig SD, Stoddard JL, Niemela JE, Tamankar V, Mhatre S, Bargir U, Kulkarni M, Shah N, Aggarwal A, Lashkari HP, Krishna V, Govindaraj G, Kalra M, Madkaikar M
Front Immunol 2019;10:23. Epub 2019 Feb 4 doi: 10.3389/fimmu.2019.00023. PMID: 30778343Free PMC Article
Michos A, Tzanoudaki M, Villa A, Giliani S, Chrousos G, Kanariou M
J Clin Immunol 2011 Oct;31(5):778-83. Epub 2011 Jul 6 doi: 10.1007/s10875-011-9564-0. PMID: 21732012
Notarangelo LD, Mella P, Jones A, de Saint Basile G, Savoldi G, Cranston T, Vihinen M, Schumacher RF
Hum Mutat 2001 Oct;18(4):255-63. doi: 10.1002/humu.1188. PMID: 11668610

Therapy

Pan Y, Pan H, Lian C, Wu B, Lin J, Huang G, Cui B
Front Immunol 2022;13:1055607. Epub 2022 Nov 17 doi: 10.3389/fimmu.2022.1055607. PMID: 36466884Free PMC Article

Prognosis

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
Michos A, Tzanoudaki M, Villa A, Giliani S, Chrousos G, Kanariou M
J Clin Immunol 2011 Oct;31(5):778-83. Epub 2011 Jul 6 doi: 10.1007/s10875-011-9564-0. PMID: 21732012
Frucht DM, Gadina M, Jagadeesh GJ, Aksentijevich I, Takada K, Bleesing JJ, Nelson J, Muul LM, Perham G, Morgan G, Gerritsen EJ, Schumacher RF, Mella P, Veys PA, Fleisher TA, Kaminski ER, Notarangelo LD, O'Shea JJ, Candotti F
Genes Immun 2001 Dec;2(8):422-32. doi: 10.1038/sj.gene.6363802. PMID: 11781709

Clinical prediction guides

Aluri J, Desai M, Gupta M, Dalvi A, Terance A, Rosenzweig SD, Stoddard JL, Niemela JE, Tamankar V, Mhatre S, Bargir U, Kulkarni M, Shah N, Aggarwal A, Lashkari HP, Krishna V, Govindaraj G, Kalra M, Madkaikar M
Front Immunol 2019;10:23. Epub 2019 Feb 4 doi: 10.3389/fimmu.2019.00023. PMID: 30778343Free PMC Article
Frucht DM, Gadina M, Jagadeesh GJ, Aksentijevich I, Takada K, Bleesing JJ, Nelson J, Muul LM, Perham G, Morgan G, Gerritsen EJ, Schumacher RF, Mella P, Veys PA, Fleisher TA, Kaminski ER, Notarangelo LD, O'Shea JJ, Candotti F
Genes Immun 2001 Dec;2(8):422-32. doi: 10.1038/sj.gene.6363802. PMID: 11781709
Brugnoni D, Notarangelo LD, Sottini A, Airò P, Pennacchio M, Mazzolari E, Signorini S, Candotti F, Villa A, Mella P, Vezzoni P, Cattaneo R, Ugazio AG, Imberti L
Blood 1998 Feb 1;91(3):949-55. PMID: 9446656

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