Deoxycytidine therapy in two patients with adenosine deaminase deficiency and severe immunodeficiency disease.
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.
Cowan
M J
MJ
Wara
D W
DW
Ammann
A J
AJ
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
D003845:Deoxycytosine Nucleotides; D003841:Deoxycytidine; C024107:2'-deoxycytidine 5'-triphosphate; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase