Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (743 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
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).
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Combined Immunodeficiencies, Severe; Combined Immunodeficiency, Severe; Immunodeficiencies, Severe Combined; Severe Combined Immunodeficiencies; Immunodeficiency Syndrome, Severe Combined; Severe Combined Immunodeficiency Syndrome; Severe Combined Immune Deficiency; Immunologic Deficiency, Severe Combined.
Where it fits in the MeSH classification
- Broader topics
- Primary Immunodeficiency Diseases; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders
- Narrower topics
- X-Linked Combined Immunodeficiency Diseases
Research landscape
PubMed indexes 4,793 records tagged with the MeSH heading “Severe Combined Immunodeficiency” (counts retrieved 2026-10-29). 748 of them (15.6%) were published from 2020 onward, and the busiest period so far is through 1999 with 1,770 records.
Reviews account for 793 records (16.5%) and meta-analyses for 3. Randomized controlled trials number 1 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 1,770 |
| 2000-2009 | 1,120 |
| 2010-2019 | 1,155 |
| 2020 onward | 748 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 793 | 16.5% |
| Meta-analyses | 3 | 0.1% |
| Randomized controlled trials | 1 | 0.0% |
Method: PubMed query "Severe Combined Immunodeficiency"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in rare and inherited diseases
Rare conditions are difficult to study: few patients means small studies, case reports and registries are common, and randomized trials are the exception. Small samples limit precision and can exaggerate effects, and cases reported in the literature may be the most severe or unusual. Evidence from many small studies is best read together. Check how patients were identified, how many were included and how long they were followed.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Gene correction for SCID-X1 in long-term hematopoietic stem cells [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Gene correction in human long-term hematopoietic stem cells (LT-HSCs) could be an effective therapy for monogenic diseases of the blood and immune system.
- Closing excerpt
- In sum, our study provides specificity, toxicity and efficacy data supportive of clinical development of genome editing to treat SCID-Xl.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (151 words)
Gene correction in human long-term hematopoietic stem cells (LT-HSCs) could be an effective therapy for monogenic diseases of the blood and immune system. Here we describe an approach for X-linked sSevere cCombined iImmunodeficiency (SCID-X1) using targeted integration of a cDNA into the endogenous start codon to functionally correct disease-causing mutations throughout the gene. Using a CRISPR-Cas9/AAV6 based strategy, we achieve up to 20% targeted integration frequencies in LT-HSCs. As measures of the lack of toxicity we observe no evidence of abnormal hematopoiesis following transplantation and no evidence of off-target mutations using a high-fidelity Cas9 as a ribonucleoprotein complex. We achieve high levels of targeting frequencies (median 45%) in CD34+ HSPCs from six SCID-X1 patients and demonstrate rescue of lymphopoietic defect in a patient derived HSPC population in vitro and in vivo. In sum, our study provides specificity, toxicity and efficacy data supportive of clinical development of genome editing to treat SCID-Xl.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30967552 · DOI · PMC6456568
Adenosine deaminase deficiency: a review [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Adenosine deaminase (ADA) deficiency leads to an accumulation of toxic purine degradation by-products, most potently affecting lymphocytes, leading to adenosine deaminase-deficient severe combined immunodeficiency.
- Closing excerpt
- This article reviews the biology, clinical presentation, diagnosis and treatment of ADA-deficiency.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (163 words)
Adenosine deaminase (ADA) deficiency leads to an accumulation of toxic purine degradation by-products, most potently affecting lymphocytes, leading to adenosine deaminase-deficient severe combined immunodeficiency. Whilst most notable affects are on lymphocytes, other manifestations include skeletal abnormalities, neurodevelopmental affects and pulmonary manifestations associated with pulmonary-alveolar proteinosis. Affected patients present in early infancy, usually with persistent infection, or with pulmonary insufficiency. Three treatment options are currently available. Initial treatment with enzyme replacement therapy may alleviate acute symptoms and enable partial immunological reconstitution, but treatment is life-long, immune reconstitution is incomplete, and the reconstituted immune system may nullify the effects of the enzyme replacement. Hematopoietic stem cell transplant has long been established as the treatment of choice, particularly where a matched sibling or well matched unrelated donor is available. More recently, the use of gene addition techniques to correct the genetic defect in autologous haematopoietic stem cells treatment has demonstrated immunological and clinical efficacy. This article reviews the biology, clinical presentation, diagnosis and treatment of ADA-deficiency.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29690908 · DOI · PMC5916829
High Incidence of Severe Combined Immunodeficiency Disease in Saudi Arabia Detected Through Combined T Cell Receptor Excision Circle and Next Generation Sequencing of Newborn Dried Blood Spots [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Severe combined immunodeficiency disease (SCID) is the most severe form of primary immunodeficiency disorders (PID).
- Closing excerpt
- In this study, we provide evidence for high incidence of SCID among Saudi population (1/2,906 live births) and demonstrate the feasibility of using T-NGS PID panel on DNA extracted from DBSs as a new reliable, rapid, and cost-effective mutation screening method for newborns with low TREC assay, which can be implemented as part of NBS programs for SCID.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (237 words)
Severe combined immunodeficiency disease (SCID) is the most severe form of primary immunodeficiency disorders (PID). T-cell receptor excision circle (TREC) copy number analysis is an efficient tool for population-based newborn screening (NBS) for SCID and other T cell lymphopenias. We sought to assess the incidence of SCID among Saudi newborn population and examine the feasibility of using targeted next generation sequencing PID gene panel (T-NGS PID) on DNA isolated from dried blood spots (DBSs) in routine NBS programs as a mutation screening tool for samples with low TREC count. Punches from 8,718 DBS collected on Guthrie cards were processed anonymously for the TREC assay. DNA was extracted from samples with confirmed low TREC count, then screened for 22q11.2 deletion syndrome by real-time polymerase chain reaction and for mutations in PID-related genes by T-NGS PID panel. Detected mutations were confirmed by Sanger sequencing. Sixteen out of the 8,718 samples were confirmed to have low TREC copy number. Autosomal recessive mutations in AK2, JAK3, and MTHFD1 were confirmed in three samples. Two additional samples were positive for the 22q11.2 deletion syndrome. In this study, we provide evidence for high incidence of SCID among Saudi population (1/2,906 live births) and demonstrate the feasibility of using T-NGS PID panel on DNA extracted from DBSs as a new reliable, rapid, and cost-effective mutation screening method for newborns with low TREC assay, which can be implemented as part of NBS programs for SCID.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29713328 · DOI · PMC5911483
The ClinGen Severe Combined Immunodeficiency Disease Variant Curation Expert Panel: Specifications for classification of variants in ADA, DCLRE1C, IL2RG, IL7R, JAK3, RAG1, and RAG2 [4]
Abstract reading summary — source excerpts
- Opening excerpt
- PurposeThis collaborative study, led by the Clinical Genome Resource Severe Combined Immunodeficiency Disease Variant Curation Expert Panel (ClinGen SCID-VCEP), implemented and adapted the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for interpreting germline variants in genes with established relationships to SCID.
- Closing excerpt
- ConclusionThe SCID-specific variant curation guidelines developed by the SCID-VCEP will enhance the precision of SCID genetic diagnosis and provide a robust framework for interpreting variants in SCID-related genes, contributing to appropriate treatment of SCID.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (192 words)
PurposeThis collaborative study, led by the Clinical Genome Resource Severe Combined Immunodeficiency Disease Variant Curation Expert Panel (ClinGen SCID-VCEP), implemented and adapted the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for interpreting germline variants in genes with established relationships to SCID. The effort focused on the 7 most common SCID-related genes identified by SCID newborn screening in North America: ADA, DCLRE1C, IL2RG, IL7R, JAK3, RAG1, and RAG2.MethodsThe SCID-VCEP conducted a rigorous review of variants that involved database analyses, literature review, and expert feedback to derive gene-specific modifications to the ACMG/AMP guidelines. These specifications were validated using a pilot set of 90 variants.ResultsOf these 90 variants, 25 were classified as pathogenic, 21 as likely pathogenic, 14 as variants of uncertain significance, 18 as likely benign, and 12 as benign. Seventeen variants with conflicting classifications in ClinVar were successfully resolved. The criteria included modifications to 20 of the 28 original ACMG/AMP criteria specific to SCID-related genes.ConclusionThe SCID-specific variant curation guidelines developed by the SCID-VCEP will enhance the precision of SCID genetic diagnosis and provide a robust framework for interpreting variants in SCID-related genes, contributing to appropriate treatment of SCID.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41104538 · DOI · PMC13175239
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Calcium signalling in lymphocyte activation and disease [5]
- Research article Diseases caused by mutations in ORAI1 and STIM1 [6]
- Research article The bare lymphocyte syndrome and the regulation of MHC expression [7]
- Research article Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution [8]
- Research article Regulation of MHC class II genes: lessons from a disease [9]
- Research article Cytokines and immunodeficiency diseases [10]
References
- Pavel-Dinu M, Wiebking V, Dejene BT, Srifa W, Mantri S, Nicolas CE, et al.. Gene correction for SCID-X1 in long-term hematopoietic stem cells. . 2019. PMID 30967552 · DOI · PMC6456568
- Flinn AM, Gennery AR. Adenosine deaminase deficiency: a review. . 2018. PMID 29690908 · DOI · PMC5916829
- Al-Mousa H, Al-Dakheel G, Jabr A, Elbadaoui F, Abouelhoda M, Baig M, et al.. High Incidence of Severe Combined Immunodeficiency Disease in Saudi Arabia Detected Through Combined T Cell Receptor Excision Circle and Next Generation Sequencing of Newborn Dried Blood Spots. . 2018. PMID 29713328 · DOI · PMC5911483
- Jacovas VC, Zelnick M, McNulty S, Ross JE, Khurana N, Pan X, et al.. The ClinGen Severe Combined Immunodeficiency Disease Variant Curation Expert Panel: Specifications for classification of variants in ADA, DCLRE1C, IL2RG, IL7R, JAK3, RAG1, and RAG2. . 2026. PMID 41104538 · DOI · PMC13175239
- Feske S. Calcium signalling in lymphocyte activation and disease. Nat Rev Immunol. 2007. PMID 17703229 · DOI
- Lacruz RS, Feske S. Diseases caused by mutations in ORAI1 and STIM1. Ann N Y Acad Sci. 2015. PMID 26469693 · DOI · PMC4692058
- Reith W, Mach B. The bare lymphocyte syndrome and the regulation of MHC expression. Annu Rev Immunol. 2001. PMID 11244040 · DOI
- Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol. 2004. PMID 15032591 · DOI
- Mach B, Steimle V, Martinez-Soria E, Reith W. Regulation of MHC class II genes: lessons from a disease. Annu Rev Immunol. 1996. PMID 8717517 · DOI
- Leonard WJ. Cytokines and immunodeficiency diseases. Nat Rev Immunol. 2001. PMID 11905829 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.