Severe Combined Immunodeficiencies - SCID

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics
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Indications for Testing

Laboratory Testing

  • Screen for underlying diseases associated with immunodeficiency
    • CBC – presence of lymphopenia; absolute lymphocyte count often <500 cells/µL
      • Normal lymphocyte count does not rule out severe combined immunodeficiencies (SCID)
    • HIV testing – rule out HIV infection
  • Screen for other immunodeficiencies
    • T-cell and B-cell immunodeficiency profile testing
      • Testing at minimum should include CD3, CD4, CD8, CD19, CD45RA, CD45RO, NK cell, and CD4:CD8 ratio
    • Neutrophil function testing
    • Quantitative immunoglobulins
    • Complement testing
    • Lymphocyte antigen and mitogen proliferation – will be abnormal
      • Test requires at least 7 days for results
  • Analyte/enzyme testing may be considered prior to genetic testing
    • Adenosine deaminase, purine nucleoside phosphorylase
  • Molecular diagnosis
    • Available for prenatal/postnatal testing for SCID
    • Genetic testing – see list in Clinical Background

Clinical Background

Severe combined immunodeficiencies (SCID) are genetic disorders characterized by blocking T-lymphocyte differentiation or function and often are associated with abnormal development of other lymphocyte lineages (B cells and NK cells).


  • Incidence – >1/50,000 births
  • Age – median 4-7 months
  • Sex – M:F, equal, except for X-linked forms

Identified Forms of SCID (based on the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency, 2013)


  • Block in T-lymphocyte differentiation or growth and variable abnormal development of other lymphocyte lineages

Clinical Presentation

  • Most newborns appear normal
  • Early onset of severe infections (earliest are Pneumocystis jirovecii, viral, also fungal, followed in many cases at 4-6 months by bacterial infection)
  • Growth failure
  • Persistent diarrhea
  • Desquamative skin rash, elevated liver enzymes, and GI bleeding
  • Occurrence of graft-versus-host disease upon exposure to maternal lymphocytes, during delivery, or by nonirradiated blood transfusion
    • Most prominent in skin and liver
    • May be associated with autoimmune thrombocytopenia or pancytopenia
    • Rejection of hematopoietic stem cell transplant from father or donors
  • Omenn syndrome – atypical SCID associated with hypomorphic mutations
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

CD4+ T-Cell Recent Thymic Emigrants (RTEs) 2010179
Method: Quantitative Flow Cytometry

Lymphocyte Subset Panel 6 - Total Lymphocyte Enumeration with CD45RA and CD45RO 0095862
Method: Quantitative Flow Cytometry

Natural Killer Cell and Natural Killer T-Cell Panel 2013805
Method: Semi-Quantitative Flow Cytometry

Natural Killer Cells Enumeration 0092404
Method: Quantitative Flow Cytometry

Lymphocyte Subset Panel 7 - Congenital Immunodeficiencies 0095899
Method: Quantitative Flow Cytometry

B-Cell Memory and Naive Panel 2008901
Method: Flow Cytometry

Immunoglobulins (IgA, IgG, IgM), Quantitative 0050630
Method: Quantitative Nephelometry

Lymphocyte Antigen and Mitogen Proliferation Panel 0096056
Method: Cell Culture


Time sensitive

Lymphocyte Antigen and Mitogen Proliferation Panel with Cytokine Response 2013117
Method: Cell Culture/Multiplex Bead Assay

Toll-Like Receptor Function 0051589
Method: Cell Culture/Quantitative Multiplex Bead Assay


Results should be interpreted in light of the individual’s clinical status

Defects in TLR3 associated with herpes simplex encephalitis may not be detected in this assay based on the reported instance of a patient with compound heterozygous mutations in TLR3 leading to decreased cytokine production in response to Poly I:C in fibroblasts but not PBMCs1

Primary Antibody Deficiency Panel, Sequencing (35 Genes) and Deletion/Duplication (26 Genes) 2011156
Method: Massively Parallel Sequencing/Exonic Oligonucleotide-based CGH Microarray


Not determined or evaluated – mutations in genes not included on the panel, deep intronic and regulatory region mutations, breakpoints for large deletions/duplications, translocations

Deletions/duplications will not be detected in IKBKG, LRBA, LRRC8A, PIK3CD, PIK3R1, PLCG2, PRKCD, SH2D1A, or XIAP/BIRC4 gene

Small deletions or insertions may not be detected

Diagnostic errors can occur due to rare sequence variations

Lack of a detectable gene mutation does not exclude a diagnosis of primary antibody deficiency


Al-Herz W, Bousfiha A, Casanova J, Chatila T, Conley ME, Cunningham-Rundles C, Etzioni A, Franco JL, Gaspar B, Holland SM, Klein C, Nonoyama S, Ochs HD, Oksenhendler E, Picard C, Puck JM, Sullivan K, Tang ML. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies expert committee for primary immunodeficiency. Front Immunol. 2014; 5: 162. PubMed

General References

Aloj G, Giardino G, Valentino L, Maio F, Gallo V, Esposito T, Naddei R, Cirillo E, Pignata C. Severe combined immunodeficiences: new and old scenarios. Int Rev Immunol. 2012; 31(1): 43-65. PubMed

Cossu F. Genetics of SCID. Ital J Pediatr. 2010; 36: 76. PubMed

Locke BA, Dasu T, Verbsky JW. Laboratory diagnosis of primary immunodeficiencies. Clin Rev Allergy Immunol. 2014; 46(2): 154-68. PubMed

Niehues T, Perez-Becker R, Schuetz C. More than just SCID--the phenotypic range of combined immunodeficiencies associated with mutations in the recombinase activating genes (RAG) 1 and 2. Clin Immunol. 2010; 135(2): 183-92. PubMed

van der Burg M, Gennery AR. Educational paper. The expanding clinical and immunological spectrum of severe combined immunodeficiency. Eur J Pediatr. 2011; 170(5): 561-71. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Augustine NH, Pasi BM, Hill HR. Comparison of ATP production in whole blood and lymphocyte proliferation in response to phytohemagglutinin. J Clin Lab Anal. 2007; 21(5): 265-70. PubMed

Shyur SD, Hill HR. Recent advances in the genetics of primary immunodeficiency syndromes. J Pediatr. 1996; 129(1): 8-24. PubMed

Medical Reviewers

Last Update: July 2017