title: Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency.
abstract: Genetic deficiency of adenosine deaminase (ADA) can cause profound lymphopenia and result in the clinical presentation of severe combined immune deficiency (SCID). However, because of the ubiquitous expression of ADA, ADA-deficient patients often present also with nonimmunologic 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 nonmyeloablative 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 www.clinicaltrials.gov as #NCT00018018 and #NCT00006319.
authors: Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA. sokolicr@mail.nih.gov
authors: Robert
authors: R
authors: Sokolic
authors: Irina
authors: I
authors: Maric
authors: Chimene
authors: C
authors: Kesserwan
authors: Elizabeth
authors: E
authors: Garabedian
authors: I Celine
authors: IC
authors: Hanson
authors: Margaret
authors: M
authors: Dodds
authors: Rebecca
authors: R
authors: Buckley
authors: Andrew C
authors: AC
authors: Issekutz
authors: Naynesh
authors: N
authors: Kamani
authors: Kit
authors: K
authors: Shaw
authors: Ben
authors: B
authors: Tan
authors: Pawan
authors: P
authors: Bali
authors: Michael S
authors: MS
authors: Hershfield
authors: Donald B
authors: DB
authors: Kohn
authors: Alan S
authors: AS
authors: Wayne
authors: Fabio
authors: F
authors: Candotti
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000150:complications* / Q000628:therapy; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007223:Infant; D008297:Male; D009190:Myelodysplastic Syndromes / Q000209:etiology* / Q000628:therapy; D016511:Severe Combined Immunodeficiency / Q000150:complications* / Q000628:therapy; D055815:Young Adult
chemical_list: D000243:Adenosine Deaminase