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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 Immune Deficiency; Severe combined immunodeficiency
SNOMED CT: Severe combined immunodeficiency (31323000); Combined T-cell and B-cell immunodeficiency (31323000); Severe combined immunodeficiency disease (31323000); SCID - severe combined immunodeficiency (31323000)
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).
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: 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.
 
Related genes: IL2RG, ADA
 
HPO: HP:0004430
Monarch Initiative: MONDO:0015974
Orphanet: ORPHA183660

Definition

A type of primary immune deficiency that is characterized by a more severe defect in both the T- and B-lymphocyte systems. [from HPO]

Term Hierarchy

Follow this link to review classifications for Severe combined immunodeficiency disease in Orphanet.

Conditions with this feature

X-linked severe combined immunodeficiency
MedGen UID:
220906
Concept ID:
C1279481
Disease or Syndrome
The phenotypic spectrum of X-linked severe combined immunodeficiency (X-SCID) ranges from typical X-SCID (early-onset disease in males that is fatal if not treated with hematopoietic stem cell transplantation [HSCT] or gene therapy) to atypical X-SCID (later-onset disease comprising phenotypes caused by variable immunodeficiency, immune dysregulation, and/or autoimmunity). Typical X-SCID. Prior to universal newborn screening (NBS) for SCID most males with typical X-SCID came to medical attention between ages three and six months because of recurrent infections, persistent infections, and infections with opportunistic organisms. With universal NBS for SCID, the common presentation for typical X-SCID is now an asymptomatic, healthy-appearing male infant. Atypical X-SCID, which usually is not detected by NBS, can manifest in the first years of life or later with one of the following: recurrent upper and lower respiratory tract infections with bronchiectasis; Omenn syndrome, a clinical phenotype caused by immune dysregulation; X-SCID combined immunodeficiency (often with recurrent infections, warts, and dermatitis); immune dysregulation and autoimmunity; or Epstein-Barr virus-related lymphoproliferative complications.
Severe combined 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). Genetic Heterogeneity of SCID 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 (SCIDX1; 300400) caused by mutation in the IL2RG gene (308380) on chromosome Xq13.1. Autosomal recessive SCID includes T-, B-, NK+ SCID, caused by mutation in the RAG1 and RAG2 genes on 11p13; T-, B+, NK- SCID (600802), caused by mutation in the JAK3 gene (600173) on 19p13; T-, B+, NK+ SCID (IMD104; 608971), caused by mutation in the IL7R gene (146661) on 5p13; T-, B+, NK+ SCID (IMD105; 619924), caused by mutation in the CD45 gene (PTPRC; 151460) on 1q31-q32; T-, B+, NK+ SCID (IMD19; 615617), caused by mutation in the CD3D gene (186790) on 11q23; T-, B-, NK- SCID (102700) caused by mutation in the ADA (608958) gene on 20q13; and T-, B-, NK+ SCID with sensitivity to ionizing radiation (602450), caused by mutation in the Artemis gene (DCLRE1C; 605988) on 10p13 (Kalman et al., 2004); and T-, B-, NK+ SCID with microcephaly, growth retardation, and sensitivity to ionizing radiation (611291), caused by mutation in the NHEJ1 gene (611290) on 2q35. 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).
T-B+ severe combined immunodeficiency due to JAK3 deficiency
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.
Absent thumb-short stature-immunodeficiency syndrome
MedGen UID:
338553
Concept ID:
C1848818
Disease or Syndrome
An exceedingly rare, autosomal recessive immune disease characterized by thumb aplasia, short stature with skeletal abnormalities, and combined immunodeficiency described in three sibships from two possibly related families. The skeletal abnormalities included unfused olecranon and the immunodeficiency manifested with severe chickenpox and chronic candidiasis. No new cases have been reported since 1978.
Short-limb skeletal dysplasia with severe combined immunodeficiency
MedGen UID:
348040
Concept ID:
C1860168
Disease or Syndrome
An extremely rare type of severe combined immunodeficiency syndrome (SCID) characterized by the classical signs of T-B- SCID (severe and recurrent infections, diarrhea, failure to thrive, absence of T and B lymphocytes) associated with skeletal anomalies like short stature, bowing of the long bones and metaphyseal abnormalities of variable degree of severity.
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase 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 due to DCLRE1C deficiency
MedGen UID:
355454
Concept ID:
C1865370
Disease or Syndrome
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.
Immunodeficiency 19
MedGen UID:
816477
Concept ID:
C3810147
Disease or Syndrome
Immunodeficiency-19 (IMD19) is an autosomal recessive form of severe combined immunodeficiency (SCID) characterized by onset in early infancy of recurrent bacterial, viral, and fungal infections. Patients usually have chronic diarrhea, recurrent respiratory infections, and failure to thrive. Immunologic work-up shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype. The disorder is lethal in early childhood without bone marrow transplantation (summary by Yu et al., 2011).
Severe combined immunodeficiency due to DNA-PKcs deficiency
MedGen UID:
863270
Concept ID:
C4014833
Disease or Syndrome
Severe combined immunodeficiency (SCID) due to DNA-PKcs deficiency is an extremely rare type of SCID (see this term) characterized by the classical signs of SCID (severe and recurrent infections, diarrhea, failure to thrive), absence of T and B lymphocytes, and cell sensitivity to ionizing radiation.
Immunodeficiency 49
MedGen UID:
934623
Concept ID:
C4310656
Disease or Syndrome
Any primary immunodeficiency disease in which the cause of the disease is a mutation in the BCL11B gene.
Immunoskeletal dysplasia with neurodevelopmental abnormalities
MedGen UID:
1381460
Concept ID:
C4479452
Disease or Syndrome
Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia
MedGen UID:
1615364
Concept ID:
C4540434
Disease or Syndrome
Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia is an inborn error of folate metabolism due to deficiency of methylenetetrahydrofolate dehydrogenase-1. Manifestations may include hemolytic uremic syndrome, macrocytosis, epilepsy, hearing loss, retinopathy, mild mental retardation, lymphopenia involving all subsets, and low T-cell receptor excision circles. Folinic acid supplementation is an effective treatment (summary by Ramakrishnan et al., 2016).
Immunodeficiency 104
MedGen UID:
1801019
Concept ID:
C5676890
Disease or Syndrome
Immunodeficiency-104 (IMD104) is an autosomal recessive disorder characterized by the onset of recurrent infections in early infancy. Manifestations may include oral thrush, fever, and failure to thrive. Some patients have lymphadenopathy and hepatosplenomegaly, whereas others have absence of lymph nodes and lack a thymic shadow. Laboratory studies show decreased or absent numbers of nonfunctional T cells, normal or increased levels of B cells, variable hypogammaglobulinemia, and normal NK cells. The disorder is caused by a defect in IL7 (146660) signaling due to a mutant IL7 receptor. Hematopoietic stem cell transplantation may be curative (Roifman et al., 2000 and Giliani et al., 2005). Giliani et al. (2005) provided a detailed review of IL7R deficiency, including discussion of the IL7R gene and its function in the immune system, clinical features of the disorder, and experiences with hematopoietic stem cell transplant as treatment. For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive SCID, see 601457.
Gastrointestinal defects and immunodeficiency syndrome 1
MedGen UID:
1806192
Concept ID:
C5680044
Disease or Syndrome
Gastrointestinal defects and immunodeficiency syndrome-1 (GIDID1) is characterized by multiple intestinal atresia, in which atresia occurs at various levels throughout the small and large intestines. Surgical outcomes are poor, and the condition is usually fatal within the first month of life. Some patients exhibit inflammatory bowel disease (IBD), with or without intestinal atresia, and in some cases, the intestinal features are associated with either mild or severe combined immunodeficiency (Samuels et al., 2013; Avitzur et al., 2014; Lemoine et al., 2014). Genetic Heterogeneity of GIDID See also GIDID2 (619708), caused by mutation in the PI4KA gene (600286) on chromosome 22q11.

Professional guidelines

PubMed

Fayez EA, Qazvini FF, Mahmoudi SM, Khoei S, Vesaltalab M, Teimourian S
Immunobiology 2020 May;225(3):151961. Epub 2020 May 20 doi: 10.1016/j.imbio.2020.151961. PMID: 32517885
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
Chien YH, Chiang SC, Chang KL, Yu HH, Lee WI, Tsai LP, Hsu LW, Hu MH, Hwu WL
J Formos Med Assoc 2015 Jan;114(1):12-6. Epub 2013 Jan 3 doi: 10.1016/j.jfma.2012.10.020. PMID: 25618583

Curated

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Severe Combined Immunodeficiency (SCID) and Conditions Associated with T Cell Lymphopenia, 2012

Recent clinical studies

Etiology

Zeng Y, Ying W, Wang W, Hou J, Liu L, Sun B, Hui X, Gu Y, Song X, Wang X, Sun J
J Clin Immunol 2023 May;43(4):756-768. Epub 2023 Jan 20 doi: 10.1007/s10875-022-01422-2. PMID: 36662455
King JR, Notarangelo LD, Hammarström L
J Allergy Clin Immunol 2021 Feb;147(2):428-438. doi: 10.1016/j.jaci.2020.12.633. PMID: 33551024Free PMC Article
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Immunobiology 2020 May;225(3):151961. Epub 2020 May 20 doi: 10.1016/j.imbio.2020.151961. PMID: 32517885
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Diagnosis

Zeng Y, Ying W, Wang W, Hou J, Liu L, Sun B, Hui X, Gu Y, Song X, Wang X, Sun J
J Clin Immunol 2023 May;43(4):756-768. Epub 2023 Jan 20 doi: 10.1007/s10875-022-01422-2. PMID: 36662455
Thomas C, Hubert G, Catteau A, Danielo M, Riche VP, Mahlaoui N, Moshous D, Audrain M
Arch Pediatr 2020 Nov;27(8):485-489. Epub 2020 Sep 11 doi: 10.1016/j.arcped.2020.08.008. PMID: 32928653
Chinn IK, Shearer WT
Immunol Allergy Clin North Am 2015 Nov;35(4):671-94. doi: 10.1016/j.iac.2015.07.002. PMID: 26454313
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
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Therapy

Blanco E, Izotova N, Booth C, Thrasher AJ
Front Immunol 2020;11:608653. Epub 2020 Nov 27 doi: 10.3389/fimmu.2020.608653. PMID: 33329605Free PMC Article
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Prognosis

Zeng Y, Ying W, Wang W, Hou J, Liu L, Sun B, Hui X, Gu Y, Song X, Wang X, Sun J
J Clin Immunol 2023 May;43(4):756-768. Epub 2023 Jan 20 doi: 10.1007/s10875-022-01422-2. PMID: 36662455
Thomas C, Hubert G, Catteau A, Danielo M, Riche VP, Mahlaoui N, Moshous D, Audrain M
Arch Pediatr 2020 Nov;27(8):485-489. Epub 2020 Sep 11 doi: 10.1016/j.arcped.2020.08.008. PMID: 32928653
Bradford KL, Liu S, Krajinovic M, Ansari M, Garabedian E, Tse J, Wang X, Shaw KL, Gaspar HB, Candotti F, Kohn DB
Biol Blood Marrow Transplant 2020 Oct;26(10):1819-1827. Epub 2020 Jul 9 doi: 10.1016/j.bbmt.2020.07.004. PMID: 32653625Free PMC Article
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
Chien YH, Chiang SC, Chang KL, Yu HH, Lee WI, Tsai LP, Hsu LW, Hu MH, Hwu WL
J Formos Med Assoc 2015 Jan;114(1):12-6. Epub 2013 Jan 3 doi: 10.1016/j.jfma.2012.10.020. PMID: 25618583

Clinical prediction guides

Bradford KL, Liu S, Krajinovic M, Ansari M, Garabedian E, Tse J, Wang X, Shaw KL, Gaspar HB, Candotti F, Kohn DB
Biol Blood Marrow Transplant 2020 Oct;26(10):1819-1827. Epub 2020 Jul 9 doi: 10.1016/j.bbmt.2020.07.004. PMID: 32653625Free PMC Article
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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
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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

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    Curated

    • ACMG ACT, 2012
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Severe Combined Immunodeficiency (SCID) and Conditions Associated with T Cell Lymphopenia, 2012

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