Blood Journal
Leading the way in experimental and clinical research in hematology

Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency

  1. Robert Sokolic1,*,
  2. Irina Maric2,
  3. Chimene Kesserwan3,
  4. Elizabeth Garabedian1,
  5. I. Celine Hanson4,
  6. Margaret Dodds4,
  7. Rebecca Buckley5,
  8. Andrew C. Issekutz6,
  9. Naynesh Kamani7,
  10. Kit Shaw8,
  11. Ben Tan9,
  12. Pawan Bali10,
  13. Michael S. Hershfield11,
  14. Donald B. Kohn8,
  15. Alan S. Wayne3, and
  16. Fabio Candotti1
  1. 1 Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, MD, United States;
  2. 2 Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States;
  3. 3 Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States;
  4. 4 Allergy and Immunology Section, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, United States;
  5. 5 Departments of Pediatrics and Immunology, Duke University Medical Center, Durham, NC, United States;
  6. 6 Department of Pediatrics, Dalhousie University, Halifax, NS, Canada;
  7. 7 Departments of Pediatrics and Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC, United States;
  8. 8 Department of Microbiology, Immunology, and Molecular Genetics, University of California - Los Angeles, Los Angeles, CA, United States;
  9. 9 University of Saskatchewan, Saskatoon, SK, Canada;
  10. 10 Department of Medicine, Duke University Medical Center, Durham, NC, United States;
  11. 11 Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC, United States
  1. * Corresponding author; email: sokolicr{at}
This article has an Erratum 123(11):1767


Genetic deficiency of adenosine deaminase (ADA) can cause profound lymphopenia and result in the clinical presentation of severe combined immune deficiency (SCID). However, due to the ubiquitous expression of ADA, ADA-deficient patients often present also with non-immunological clinical problems, affecting the skeletal, central nervous, endocrine and gastrointestinal systems. We now report that myeloid dysplasia features and bone marrow hypocellularity are often found in patients with ADA-SCID. As a clinical correlate to this finding, we have observed vulnerability to antibiotic-induced myelotoxicity and prolonged neutropenia after non-myeloablative chemotherapy. We have also noted that, in the absence of enzyme replacement therapy, absolute neutrophil counts of patients with ADA deficiency vary inversely with the accumulation of deoxynucleotides. These data have significant implications for the application of standard and investigational therapies to patients with ADA-SCID and support further studies to investigate the possibility that ADA deficiency is associated with a stem cell defect. These trials were registered at as NCT00018018, NCT00006319.

  • Submitted January 7, 2011.
  • Accepted May 30, 2011.