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Adenosine Deaminase (ADA)–Deficient Severe Combined Immune Deficiency (SCID) in the US Immunodeficiency Network (USIDNet) Registry

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Abstract

Clinical data from ADA-SCID patients registered in the U.S. Immunodeficiency Network (USIDNet) Repository were analyzed. Sixty-four ADA-SCID patients born between 1981 and 2017 had clinical data entered by their local (or home) enrolling institution. Median age at diagnosis was 1 month for those with a positive family history and 3 months for those without a prior family history, with some diagnosed at birth and one as late as 9 years of age. Overall survival was 79.7%, which increased to 94.1% since 2010. These patients had multiple infections and pulmonary, gastrointestinal, and neurological complications. The majority received enzyme replacement therapy (ERT) at some time, including 88% of those born since 2010. Twenty-six patients underwent allogeneic hematopoietic stem cell transplant (HSCT). HSCT successfully supported survival (17/26, 65%) using a variety of cell sources (bone marrow, mobilized peripheral blood, and cord blood) from sibling, family and unrelated donors. Nineteen patients underwent autologous HSCT with gene therapy (GT) using retroviral and lentiviral vectors and all are surviving. The prognosis for patients with ADA-SCID has continued to improve but these patients do have multiple early and potentially long-term conditions that require medical monitoring and management.

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References

  1. Santisteban I, Arredondo-Vega FX, Kelly S, Mary A, Fischer A, Hummell DS, et al. Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease: contribution of genotype to phenotype. J Clin Invest. 1993;92(5):2291–302.

    Article  CAS  Google Scholar 

  2. Shovlin CL, et al. Adult presentation of adenosine deaminase deficiency. Lancet. 1993;38(6):1253–65.

    Google Scholar 

  3. Umetsu DT, Schlossman CM, Ochs HD, Hershfield MS. Heterogeneity of phenotype in two siblings with adenosine deaminase deficiency. J Allergy Clin Immunol. 1994;93(2):543–50.

    Article  CAS  Google Scholar 

  4. Bradford KL, Moretti FA, Carbonaro-Sarracino DA, Gaspar HB, Kohn DB. Adenosine deaminase (ADA)-deficient severe combined immune deficiency (SCID): molecular pathogenesis and clinical manifestations. J Clin Immunol. 2017;37(7):626–37.

    Article  CAS  Google Scholar 

  5. Kohn DB, Hershfield MS, Puck JM, Aiuti A, Blincoe A, Gaspar HB, et al. Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency. J Allergy Clin Immunol. 2019;143(3):852–63.

    Article  Google Scholar 

  6. Cicalese MP, Ferrua F, Castagnaro L, Rolfe K, de Boever E, Reinhardt RR, et al. Gene therapy for adenosine deaminase deficiency: a comprehensive evaluation of short- and medium-term safety. Mol Ther. 2018;26(3):917–31.

    Article  CAS  Google Scholar 

  7. Kohn DB, Gaspar HB. How we manage adenosine deaminase-deficient severe combined immune deficiency (ADA SCID). J Clin Immunol. 2017;37(4):351–6.

    Article  CAS  Google Scholar 

  8. Buckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, et al. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. 1997;130(3):378–87.

    Article  CAS  Google Scholar 

  9. Kwan A, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2015;312(7):729–38.

    Article  Google Scholar 

  10. Nofech-Mozes Y, Blaser SI, Kobayashi J, Grunebaum E, Roifman CM. Neurologic abnormalities in patients with adenosine deaminase deficiency. Pediatr Neurol. 2007;37(3):218–21.

    Article  Google Scholar 

  11. Pai S-Y, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, et al. Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med. 2014;371(5):434–46.

    Article  CAS  Google Scholar 

  12. Hönig M, et al. Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications. Blood. 2007;109(8):3595–602.

    Article  Google Scholar 

  13. Rogers MH, Lwin R, Fairbanks L, Gerritsen B, Gaspar HB. Cognitive and behavioral abnormalities in adenosine deaminase deficient severe combined immunodeficiency. J Pediatr. 2001;139(1):44–50.

    Article  CAS  Google Scholar 

  14. Sauer AV, et al. Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients. Sci Rep. 2016;7:1–13.

    Google Scholar 

Download references

Acknowledgments

We acknowledge Hannah Wright (USIDNet Research Data Analyst) and Julieann Magnusson (USIDNet Project Manager) for their expertise in data management and aid in obtaining and analyzing the data. We also thank Dr. Mary Ellen Conley and Dr. Vivian Hernandez-Trujillo for providing additional patient information through chart review.

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Authors and Affiliations

  1. Division of Allergy & Immunology, Department of Pediatrics, David Geffen School of Medicine at the University of California, Los Angeles, 10833 Le Conte, MDCC 12-430, Los Angeles, CA, 90095, USA

    Caroline Y. Kuo

  2. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Elizabeth Garabedian

  3. Allergy Immunology and Blood and Marrow Transplant Division, Department of Pediatrics, University of California San Francisco Benioff Children’s Hospital, San Francisco, CA, 94143, USA

    Jennifer Puck & Morton J. Cowan

  4. Division of Allergy and Immunology, The Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Kathleen E. Sullivan

  5. Departments of Pediatrics and Immunology, Duke University Medical Center, Durham, NC, 27708, USA

    Rebecca H. Buckley

  6. Departments of Medicine and Pediatrics, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Charlotte Cunningham-Rundles

  7. Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA

    Rebecca Marsh

  8. Departments of Medicine, School of Medicine and Biology, University of Lausanne, Lausanne, Switzerland

    Fabio Candotti

  9. Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA

    Donald B. Kohn

  10. Division of Hematology & Oncology, Department of Pediatrics, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, 90095, USA

    Donald B. Kohn

Authors
  1. Caroline Y. Kuo
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  2. Elizabeth Garabedian
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  3. Jennifer Puck
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  4. Morton J. Cowan
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  5. Kathleen E. Sullivan
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  6. Rebecca H. Buckley
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  7. Charlotte Cunningham-Rundles
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  8. Rebecca Marsh
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  9. Fabio Candotti
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  10. Donald B. Kohn
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Correspondence to Caroline Y. Kuo.

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Kuo, C.Y., Garabedian, E., Puck, J. et al. Adenosine Deaminase (ADA)–Deficient Severe Combined Immune Deficiency (SCID) in the US Immunodeficiency Network (USIDNet) Registry. J Clin Immunol 40, 1124–1131 (2020). https://doi.org/10.1007/s10875-020-00857-9

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  • DOI: https://doi.org/10.1007/s10875-020-00857-9

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