A Review on Types and Treatment Strategies of Severe Combined Immunodeficiency
Abstract
Severe Combined Immunodeficiency (SCID) is a rare and life-threatening congenital disorder affecting the immune system's functionality due to mutations in crucial genes involved in immune cell development. This review provides a comprehensive overview of SCID, covering its genetic basis, immune system components, clinical manifestations, diagnostic methods, and treatment strategies. The review emphasizes the importance of early detection through newborn screening, enabling prompt treatment and enhancing survival rates for individuals with SCID. SCID can be classified as Typical, Atypical which also includes Omenn Syndrome, atypical/leaky, variant. Gene mutations with various severe infections, diarrhea, lack of T cells, reduction in naive T cells, increase in T cells and absence of proliferative responses to mitogens, or T cells with a maternal ancestry are all characteristics of typical SCID. About a dozen genes, which together make up the rare genetic condition SCID, are chiefly responsible for its X-linked or autosomal recessive inheritance. Due to infrequent incidences, early detection and treatment may go unnoticed. CD3+ > 300 cells/L and a diminished, but discernible, proliferative response to PHA (>10-30% of the control) are characteristics of atypical SCID. Other names for it include "leaky SCID”. When there is no known gene issue and there are still 300–1500 T cells per liter with reduced function, variant SCID is diagnosed. The treatment options available to treat SCID are bone marrow transplantation also known as hematopoietic stem cell transplant (HSCT), gene therapy, enzyme replacement therapy, gamma globulins etc. The most widely used treatment with a high success rate is bone marrow transplantation (BMT), which can enable the body to once again create those vital infection-fighting cells. Blood cell production occurs in the bone marrow. Most SCID children pass away before they are two without a BMT.
Keywords: Bubble boy disease, gene therapy, hematopoietic stem cell transplantation (HSCT), bone marrow transplantation (BMT), Enzyme replacement therapy (ERT).
Keywords:
Bubble boy disease, gene therapy, hematopoietic stem cell transplantation (HSCT), bone marrow transplantation (BMT), Enzyme replacement therapy (ERT)DOI
https://doi.org/10.22270/jddt.v15i3.7031References
1. Vaillant AA, Mohseni M. Severe combined immunodeficiency. InStatPearls [Internet] 2023 Aug 8. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK539762/
2. Al Sukaiti N, Ahmed K, Al Shekaili J, Al Kindi M, Cook MC, Farsi TA. A decade experience on severe combined immunodeficiency phenotype in Oman, bridging to newborn screening. Frontiers in Immunology. 2021 Jan 15; 11:623199. https://doi.org/10.3389/fimmu.2020.623199 PMid:33519828 PMCid:PMC7844122
3. S. Srakocic.Severe combined immunodeficiency. Healthline; 2023 [cited 2025 Feb 15]. https://www.healthline.com/health/severe-combined-immunodeficiency .
4. Rivers L, Gaspar HB. Severe combined immunodeficiency: recent developments and guidance on clinical management. Archives of disease in childhood. 2015 Jul 1;100(7):667-672. https://doi.org/10.1136/archdischild-2014-306425 PMid:25564533
5. Lisa Vawter, Eric Allenspach et al. Severe Combined Immunodeficiency. NORD. January 02, 2019.https://rarediseases.org/rare-diseases/severe-combined-immunodeficiency/
6. Justiz-Vaillant AA, Gopaul D, Akpaka PE, Soodeen S, Arozarena Fundora R. Severe Combined Immunodeficiency-Classification, Microbiology Association and Treatment. Microorganisms. 2023 Jun 15;11(6):1589. https://doi.org/10.3390/microorganisms11061589 PMid:37375091 PMCid:PMC10304095
7. Villa A, Moshous D, de Villartay JP, Notarangelo LD, Candotti F. Severe Combined Immunodeficiencies. InStiehm's Immune Deficiencies 2014 Jan 1 (pp. 87-141). Academic Press. https://doi.org/10.1016/B978-0-12-405546-9.00004-2 PMid:25010321
8. Pai SY, Thrasher AJ. Gene therapy for X-linked severe combined immunodeficiency: historical outcomes and current status. Journal of Allergy and Clinical Immunology. 2020 Aug 1;146(2):258-61. https://doi.org/10.1016/j.jaci.2020.05.055 PMid:32561390
9. Flinn AM, Gennery AR. Adenosine deaminase deficiency: a review. Orphanet journal of rare diseases. 2018 Dec;13:1-7.DOI: 10.1186/s13023-018-0807-5 https://doi.org/10.1186/s13023-018-0807-5 PMid:29690908 PMCid:PMC5916829
10. Gennery A. Recent advances in understanding RAG deficiencies. F1000Research. 2019 Feb 4;8: https://doi.org/10.12688/f1000research.17056.1 PMid:30800289 PMCid:PMC6364374
11. Liao CY, Yu HW, Cheng CN, Chen JS, Lin CW, Chen PC, Shieh CC. A novel pathogenic mutation on Interleukin-7 receptor leading to severe combined immunodeficiency identified with newborn screening and whole exome sequencing. Journal of Microbiology, Immunology and Infection. 2020 Feb 1;53(1):99-105. https://doi.org/10.1016/j.jmii.2018.02.003 PMid:29551298
12. Butte MJ, Haines C, Bonilla FA, Puck J. IL-7 receptor deficient SCID with a unique intronic mutation and post-transplant autoimmunity due to chronic GVHD. Clinical Immunology. 2007 Nov 1;125(2):159-64. https://doi.org/10.1016/j.clim.2007.06.007 PMid:17827065 PMCid:PMC2100404
13. Fischer A, de Saint Basile G, et al. CD3 complex deficiencies. Immunodeficiency Search. https://www.immunodeficiencysearch.com/cd3-complex-deficiencies
14. Boxall S, Stanton T, Hirai K, Ward V, Yasui T, Tahara H, Tamori A, Nishiguchi S, Shiomi S, Ishiko O, Inaba M. Disease associations and altered immune function in CD45 138G variant carriers. Human molecular genetics. 2004 Oct 15;13(20):2377-2384. https://doi.org/10.1093/hmg/ddh276 PMid:15333587
15. Roberts JL, Buckley RH, Luo B, Pei J, Lapidus A, Peri S, Wei Q, Shin J, Parrott RE, Dunbrack Jr RL, Testa JR. CD45-deficient severe combined immunodeficiency caused by uniparental disomy. Proceedings of the National Academy of Sciences. 2012 Jun 26;109(26):10456-10461. https://doi.org/10.1073/pnas.1202249109 PMid:22689986 PMCid:PMC3387083
16. Candotti F, de Villartay JP, Moshous D, Villa A, Notarangelo LD. Severe combined immune deficiency. InStiehm's immune deficiencies 2020 Jan 1 (pp. 153-205). Academic Press. https://doi.org/10.1016/B978-0-12-816768-7.00007-7
17. Hoenig M, Lagresle-Peyrou C, Pannicke U, Notarangelo LD, Porta F, Gennery AR, Slatter M, Cowan MJ, Stepensky P, Al-Mousa H, Al-Zahrani D. Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome. Blood, The Journal of the American Society of Hematology. 2017 May 25;129(21):2928-2938. https://doi.org/10.1182/blood-2016-11-745638 PMid:28331055 PMCid:PMC5445572
18. Schwartz RA, Lin RY, et al. Omenn syndrome: background, pathophysiology, epidemiology [Internet]. Medscape; https://emedicine.medscape.com/article/887687-overview .
19. Elnour IB, Ahmed S, Halim K, Nirmala V. Omenn's Syndrome: A rare primary immunodeficiency disorder. Sultan Qaboos University Medical Journal. 2007 Aug;7(2):133.
20. Çipe FE, Aydogmus C, Babayigit Hocaoglu A, Kilic M, Kaya GD, Yilmaz Gulec E. Cernunnos/XLF deficiency: a syndromic primary immunodeficiency. Case Reports in Pediatrics. 2014;2014(1):614238. https://doi.org/10.1155/2014/614238 PMid:24511403 PMCid:PMC3910469
21. Dinur Schejter Y, Mandola A, Merico D, Reid B. Coronin 1A deficiency identified by newborn screening for severe combined immunodeficiency. LymphoSign Journal. 2019 Feb 22;6(1):17-25. https://doi.org/10.14785/lymphosign-2019-0001
22. Yee CS, Massaad MJ, Bainter W, Ohsumi TK, Föger N, Chan AC, Akarsu NA, Aytekin C, Ayvaz DÇ, Tezcan I, Sanal Ö. Recurrent viral infections associated with a homozygous CORO1A mutation that disrupts oligomerization and cytoskeletal association. Journal of Allergy and Clinical Immunology. 2016 Mar 1;137(3):879-888. https://doi.org/10.1016/j.jaci.2015.08.020 PMid:26476480 PMCid:PMC4783242
23. Volk T, Pannicke U, Reisli I, Bulashevska A, Ritter J, Björkman A, Schäffer AA, Fliegauf M, Sayar EH, Salzer U, Fisch P. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency. Human molecular genetics. 2015 Dec 20;24(25):7361-7372. https://doi.org/10.1093/hmg/ddv437 PMid:26476407 PMCid:PMC4664172
24. Moshous D, Callebaut I, De Chasseval R, Corneo B, Cavazzana-Calvo M, Le Deist F, Tezcan I, Sanal O, Bertrand Y, Philippe N, Fischer A. Artemis, a novel DNA double-strand break repair/V (D) J recombination protein, is mutated in human severe combined immune deficiency. Cell. 2001 Apr 20;105(2):177-186. https://doi.org/10.1016/S0092-8674(01)00309-9 PMid:11336668
25. Iyengar JJ, Quinonez SC, Razumilava N, Soyster B, Smith YR, Vander Lugt MT, Wyckoff J. DNA Ligase Iv Syndrome: a rare cause of growth failure & hypogonadism. AACE Clinical Case Reports. 2019 Mar 1;5(2): e154-e158. https://doi.org/10.4158/ACCR-2018-0291 PMid:31967023 PMCid:PMC6873855
26. Bacchelli C, Moretti FA, Carmo M, Adams S, Stanescu HC, Pearce K, Madkaikar M, Gilmour KC, Nicholas AK, Woods CG, Kleta R. Mutations in linker for activation of T cells (LAT) lead to a novel form of severe combined immunodeficiency. Journal of Allergy and Clinical Immunology. 2017 Feb 1;139(2):634-642. https://doi.org/10.1016/j.jaci.2016.05.036 PMid:27522155
27. Sriaroon P. Management of Immunodeficiency, Quality of Life. InEncyclopedia of Medical Immunology: Immunodeficiency Diseases 2020 Nov 5 (pp. 469-471). New York, NY: Springer New York. https://doi.org/10.1007/978-1-4614-8678-7_84
28. Ginn SL, Curtin JA, Smyth CM, Latham M, Cunningham SC, Zheng M, Hobson L, Rowe PB, Alexander IE, Kramer B, Wong M. Treatment of an infant with X‐linked severe combined immunodeficiency (SCID‐X1) by gene therapy in Australia. Medical journal of Australia. 2005 May;182(9):458-463. https://doi.org/10.5694/j.1326-5377.2005.tb06785.x PMid:15865589
29. Fernandez J, et al. Severe combined immunodeficiency (SCID) [Internet]. MSD Manual; 2023. https://www.msdmanuals.com/en-in/home/immune-disorders/immunodeficiency-disorders/severe-combined-immunodeficiency-scid
30. Kwan A, Hu D, Song M, Gomes H, Brown DR, Bourque T, Gonzalez-Espinosa D, Lin Z, Cowan MJ, Puck JM. Successful newborn screening for SCID in the Navajo Nation. Clinical Immunology. 2015 May 1;158(1): 29-34. https://doi.org/10.1016/j.clim.2015.02.015 PMid:25762520 PMCid:PMC4420660
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