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

Robert Sokolic, Irina Maric, Chimene Kesserwan, Elizabeth Garabedian, I. Celine Hanson, Margaret Dodds, Rebecca Buckley, Andrew C. Issekutz, Naynesh Kamani, Kit Shaw, Ben Tan, Pawan Bali, Michael S. Hershfield, Donald B. Kohn, Alan S. Wayne and Fabio Candotti
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.