title: Deoxycytidine therapy in two patients with adenosine deaminase deficiency and severe immunodeficiency disease.
abstract: Two children with adenosine deaminase (ADA) deficiency and combined immunodeficiency disease were given parenteral deoxycytidine in order to reverse the severe T-cell immunodeficiency associated with this disease. One patient received a total of three courses of parenteral deoxycytidine. On two occasions deoxycytidine (50 mg/kg/day) was infused intravenously continuously for 2 weeks. During one of the infusions she received the deoxycytidine deaminase inhibitor tetrahydrouridine (THU). Steady-state levels of plasma deoxycytidine increased 4-fold with THU. RBC dCTP/dATP increased more than 10-fold after 48 hr of deoxycytidine infusion. Immunologic studies following the intravenous infusion of deoxycytidine showed transient improvement in T-cell immunity. The third course of deoxycytidine (50 mg/kg/day) was administered subcutaneously during a 10-hr night-time infusion. After 6 and 12 weeks of nightly subcutaneous infusions, there was minimal improvement in the in vitro immunologic studies and no clinical improvement. The second patient received a single 2-week course of continuous intravenous deoxycytidine (50 mg/kg/day) following which there was no significant change in T-cell immunity. This study defines some of the pharmacologic parameters of human deoxycytidine metabolism and suggests that some patients with ADA deficiency may respond to deoxycytidine therapy with improvement in T-cell-mediated immunity, although the changes are small and the effect on clinical status appears to be limited.
authors.forename: M J
authors.initials: MJ
authors.lastname: Cowan
authors.forename: D W
authors.initials: DW
authors.lastname: Wara
authors.forename: A J
authors.initials: AJ
authors.lastname: Ammann
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000378:metabolism; D002675:Child, Preschool; D003841:Deoxycytidine / Q000097:blood / Q000627:therapeutic use*; D003845:Deoxycytosine Nucleotides / Q000097:blood; D004912:Erythrocytes / Q000032:analysis / Q000201:enzymology; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy*; D007223:Infant; D007958:Leukocyte Count; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D009700:Nucleoside Deaminases / Q000172:deficiency*; D013601:T-Lymphocytes
chemical_list: D003845:Deoxycytosine Nucleotides; D003841:Deoxycytidine; C024107:2'-deoxycytidine 5'-triphosphate; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase