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Severe combined immunodeficiency disease(SCID)

MedGen UID:
88328
Concept ID:
C0085110
Disease or Syndrome
Synonyms: Bubble boy disease; SCID; Severe combined immunodeficiency; Severe combined immunodeficiency due to adenosine deaminase deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
X-linked recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: SCID - Severe combined immunodeficiency (31323000); Severe combined immunodeficiency (31323000); Combined T-cell and B-cell immunodeficiency (31323000); Severe combined immunodeficiency disease (31323000); SCID (31323000)
 
Related genes: IL2RG, ADA
HPO: HP:0004430
Orphanet: ORPHA183660

Definition

Group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. It is inherited as an X-linked or autosomal recessive defect. Mutations occurring in many different genes cause human Severe Combined Immunodeficiency (SCID). [from MeSH]

Conditions with this feature

X-linked severe combined immunodeficiency
MedGen UID:
220906
Concept ID:
C1279481
Disease or Syndrome
X-linked severe combined immunodeficiency (X-SCID) is a combined cellular and humoral immunodeficiency caused by a hemizygous pathogenic variant in IL2RG. In typical X-SCID lack of IL2RG function results in near-complete absence of T and natural killer (NK) lymphocytes and nonfunctional B lymphocytes. X-SCID is almost universally fatal in the first two years of life unless reconstitution of the immune system is achieved through bone marrow transplant or gene therapy. In the absence of family history of X-SCID and prior to newborn screening for X-SCID, most males with typical X-SCID come to medical attention between ages three and six months with failure to thrive, oral/diaper candidiasis, absent tonsils and lymph nodes, recurrent infections, infections with opportunistic organisms such as Pneumocystis, and persistence of infections despite conventional treatment. Additional common features include rashes, diarrhea, cough and congestion, fevers, pneumonia, sepsis, and other severe bacterial infections. Males with atypical X-SCID may have immune dysregulation and autoimmunity associated with rashes, gastrointestinal malabsorption, and short stature.
Severe immunodeficiency, autosomal recessive, T-cell negative, B-cell negative, NK cell-positive
MedGen UID:
321935
Concept ID:
C1832322
Disease or Syndrome
Severe combined immunodeficiency refers to a genetically and clinically heterogeneous group of disorders with defective cellular and humoral immune function. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms, including Candida albicans, Pneumocystis carinii, and cytomegalovirus, among many others. Laboratory analysis shows profound lymphopenia with diminished or absent immunoglobulins. The common characteristic of all types of SCID is absence of T cell-mediated cellular immunity due to a defect in T-cell development. Without treatment, patients usually die within the first year of life. The overall prevalence of all types of SCID is approximately 1 in 75,000 births (Fischer et al., 1997; Buckley, 2004). SCID can be divided into 2 main classes: those with B lymphocytes (B+ SCID) and those without (B- SCID). Presence or absence of NK cells is variable within these groups. The most common form of SCID is X-linked T-, B+, NK- SCID (300400) caused by mutation in the IL2RG gene (308380) on chromosome Xq13.1. Autosomal recessive SCID includes T-, B+, NK- SCID (600802) caused by mutation in the JAK3 gene (600173) on 19p13.1; T-, B+, NK+ SCID (608971) caused by mutation in the IL7R gene (146661) on 5p13, the CD45 gene (151460) on 1q31-q32, or the CD3D gene (186790) on 11q23; T-, B-, NK- SCID (102700) caused by mutation in the ADA (608958) gene on 20q13.11; T-, B-, NK+ SCID with sensitivity to ionizing radiation caused by mutation in the Artemis gene on 10p; and T-, B-, NK+ SCID caused by mutation in the RAG1 and RAG2 genes on 11p13 (Kalman et al., 2004). Approximately 20 to 30% of all SCID patients are T-, B-, NK+, and approximately half of these patients have mutations in the RAG1 or RAG2 genes (Schwarz et al., 1996; Fischer et al., 1997).
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-negative
MedGen UID:
331474
Concept ID:
C1833275
Disease or Syndrome
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.
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive
MedGen UID:
373235
Concept ID:
C1837028
Disease or Syndrome
Thumb agenesis, short stature, and immunodeficiency
MedGen UID:
338553
Concept ID:
C1848818
Disease or Syndrome
Achondroplasia and severe combined immunodeficiency
MedGen UID:
348040
Concept ID:
C1860168
Disease or Syndrome
Severe combined immunodeficiency due to ADA deficiency
MedGen UID:
354935
Concept ID:
C1863236
Disease or Syndrome
Adenosine deaminase (ADA) deficiency is a systemic purine metabolic disorder that primarily affects lymphocyte development, viability, and function. The clinical phenotypic spectrum includes: Severe combined immunodeficiency disease (SCID), often diagnosed by age six months and usually by age 12 months; Less severe "delayed" onset combined immune deficiency (CID), usually diagnosed between age one and ten years; "Late/adult onset" CID, diagnosed in the second to fourth decades; Benign "partial ADA deficiency" (very low or absent ADA activity in erythrocytes but greater ADA activity in nucleated cells), which is compatible with normal immune function. Infants with typical early-onset ADA-deficient SCID have failure to thrive and opportunistic infections associated with marked depletion of T, B, and NK lymphocytes, and an absence of both humoral and cellular immune function. If immune function is not restored, children with ADA-deficient SCID rarely survive beyond age one to two years. Infections in delayed- and late-onset types (commonly, recurrent otitis, sinusitis, and upper respiratory) may initially be less severe than those in individuals with ADA-deficient SCID; however, by the time of diagnosis these individuals often have chronic pulmonary insufficiency and may have autoimmune phenomena (cytopenias, anti-thyroid antibodies), allergies, and elevated serum concentration of IgE. The longer the disorder goes unrecognized, the more immune function deteriorates and the more likely are chronic sequelae of recurrent infection.
Severe combined immunodeficiency with sensitivity to ionizing radiation
MedGen UID:
355454
Concept ID:
C1865370
Disease or Syndrome
Immunodeficiency 26 with or without neurologic abnormalities
MedGen UID:
863270
Concept ID:
C4014833
Disease or Syndrome
Immunodeficiency 49
MedGen UID:
934623
Concept ID:
C4310656
Disease or Syndrome

Recent clinical studies

Etiology

Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O'Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ
J Allergy Clin Immunol 2014 Apr;133(4):1092-8. Epub 2013 Nov 28 doi: 10.1016/j.jaci.2013.09.044. PMID: 24290292Free PMC Article
Li L, Zhou Y, Wang J, Hu D, Cowan MJ
Prenat Diagn 2002 Sep;22(9):763-8. doi: 10.1002/pd.400. PMID: 12224067
O'Marcaigh AS, DeSantes K, Hu D, Pabst H, Horn B, Li L, Cowan MJ
Bone Marrow Transplant 2001 Apr;27(7):703-9. doi: 10.1038/sj.bmt.1702831. PMID: 11360109
Hoyle C, Bangs CD, Chang P, Kamel O, Mehta B, Negrin RS
Blood 1998 Nov 1;92(9):3318-27. PMID: 9787169
Li L, Drayna D, Hu D, Hayward A, Gahagan S, Pabst H, Cowan MJ
Am J Hum Genet 1998 Jan;62(1):136-44. doi: 10.1086/301688. PMID: 9443881Free PMC Article

Diagnosis

van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM
J Clin Immunol 2015 May;35(4):416-30. Epub 2015 Apr 17 doi: 10.1007/s10875-015-0152-6. PMID: 25893636Free PMC Article
Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O'Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ
J Allergy Clin Immunol 2014 Apr;133(4):1092-8. Epub 2013 Nov 28 doi: 10.1016/j.jaci.2013.09.044. PMID: 24290292Free PMC Article
Janik DK, Lindau-Shepard B, Comeau AM, Pass KA
Clin Chem 2010 Sep;56(9):1460-5. Epub 2010 Jul 21 doi: 10.1373/clinchem.2010.144329. PMID: 20660143Free PMC Article
Dvorak CC, Cowan MJ
Immunol Allergy Clin North Am 2010 Feb;30(1):125-42. doi: 10.1016/j.iac.2009.10.004. PMID: 20113890Free PMC Article
Dvorak CC, Hung GY, Horn B, Dunn E, Oon CY, Cowan MJ
Biol Blood Marrow Transplant 2008 Oct;14(10):1125-1133. doi: 10.1016/j.bbmt.2008.07.008. PMID: 18804042

Therapy

Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O'Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ
J Allergy Clin Immunol 2014 Apr;133(4):1092-8. Epub 2013 Nov 28 doi: 10.1016/j.jaci.2013.09.044. PMID: 24290292Free PMC Article
Cossellu G, Seramondi R, Benedicenti S, Farronato G, Olivi G, Angiero F
Eur J Paediatr Dent 2013 Dec;14(4):328-32. PMID: 24313588
Dvorak CC, Hung GY, Horn B, Dunn E, Oon CY, Cowan MJ
Biol Blood Marrow Transplant 2008 Oct;14(10):1125-1133. doi: 10.1016/j.bbmt.2008.07.008. PMID: 18804042
Atluri S, Neville K, Davis M, Robertson KA, Marshalleck FE, O'Malley DP, Buckley RH, Nelson RP Jr
J Pediatr Hematol Oncol 2007 Mar;29(3):166-72. doi: 10.1097/MPH.0b013e31803b95b3. PMID: 17356396
Staflin K, Järnum S, Hua J, Honeth G, Kannisto P, Lindvall M
Int J Gynecol Cancer 2006 Jul-Aug;16(4):1557-64. doi: 10.1111/j.1525-1438.2006.00627.x. PMID: 16884365

Prognosis

van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM
J Clin Immunol 2015 May;35(4):416-30. Epub 2015 Apr 17 doi: 10.1007/s10875-015-0152-6. PMID: 25893636Free PMC Article
Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O'Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ
J Allergy Clin Immunol 2014 Apr;133(4):1092-8. Epub 2013 Nov 28 doi: 10.1016/j.jaci.2013.09.044. PMID: 24290292Free PMC Article
Dvorak CC, Hung GY, Horn B, Dunn E, Oon CY, Cowan MJ
Biol Blood Marrow Transplant 2008 Oct;14(10):1125-1133. doi: 10.1016/j.bbmt.2008.07.008. PMID: 18804042
Atluri S, Neville K, Davis M, Robertson KA, Marshalleck FE, O'Malley DP, Buckley RH, Nelson RP Jr
J Pediatr Hematol Oncol 2007 Mar;29(3):166-72. doi: 10.1097/MPH.0b013e31803b95b3. PMID: 17356396
Li L, Zhou Y, Wang J, Hu D, Cowan MJ
Prenat Diagn 2002 Sep;22(9):763-8. doi: 10.1002/pd.400. PMID: 12224067

Clinical prediction guides

van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM
J Clin Immunol 2015 May;35(4):416-30. Epub 2015 Apr 17 doi: 10.1007/s10875-015-0152-6. PMID: 25893636Free PMC Article
Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O'Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ
J Allergy Clin Immunol 2014 Apr;133(4):1092-8. Epub 2013 Nov 28 doi: 10.1016/j.jaci.2013.09.044. PMID: 24290292Free PMC Article
Atluri S, Neville K, Davis M, Robertson KA, Marshalleck FE, O'Malley DP, Buckley RH, Nelson RP Jr
J Pediatr Hematol Oncol 2007 Mar;29(3):166-72. doi: 10.1097/MPH.0b013e31803b95b3. PMID: 17356396
Ebeling P, Bach P, Sorg U, Schneider A, Trarbach T, Dilloo D, Hanenberg H, Niesert S, Seeber S, Moritz T, Flasshove M
J Cancer Res Clin Oncol 2007 Mar;133(3):199-209. Epub 2006 Oct 20 doi: 10.1007/s00432-006-0158-9. PMID: 17053889
Li L, Zhou Y, Wang J, Hu D, Cowan MJ
Prenat Diagn 2002 Sep;22(9):763-8. doi: 10.1002/pd.400. PMID: 12224067

Recent systematic reviews

van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM
J Clin Immunol 2015 May;35(4):416-30. Epub 2015 Apr 17 doi: 10.1007/s10875-015-0152-6. PMID: 25893636Free PMC Article
Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O'Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ
J Allergy Clin Immunol 2014 Apr;133(4):1092-8. Epub 2013 Nov 28 doi: 10.1016/j.jaci.2013.09.044. PMID: 24290292Free PMC Article
Cowan MJ, Neven B, Cavazanna-Calvo M, Fischer A, Puck J
Biol Blood Marrow Transplant 2008 Jan;14(1 Suppl 1):73-5. doi: 10.1016/j.bbmt.2007.10.017. PMID: 18162224

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