DIFFERENCES IN PURINE METABOLISM IN PATIENTS WITH DOWNS-SYNDROME

Three enzymes intervening in de novo purine synthesis, as well as cyst athionine B-synthetase, have been mapped to chromosome 21. In order to pin a better understanding of purine synthesis anomalies in Down's sy ndrome, the present authors studied the variations in mitotic index of lymphocyte cultures to which various inhibitors or metabolites of pur ine synthesis had been added. In spite of common gene dosage effects, unexpected and highly significant differences were noted between Down' s syndrome patients without complications and those presenting with ad ditional psychotic features. In Down's syndrome patients without compl ications, a highly significant decrease in mitotic index was noted in the presence of exogenous inosine. A significant decrease in the prese nce of adenosine and guanosine was also noted. These findings are in k eeping with the expected metabolic repercussions of genes mapped to ch romosome 2 1. In Down's syndrome patients with psychotic complications , the in vitro reactions were quite different. A paradoxal increase in mitotic index was noted in the presence of inosine and of adenosine, but the response to guanosine did not differ from that observed in nor mal controls. These findings were unexpected and seem to indicate that , in spite of the gene dosage effect, psychotic Down's syndrome patien ts are unable to compensate abnormal purine synthesis and resulting im balances. Furthermore, a marked difference in purine metabolic reactio ns was noted between Down's syndrome patients receiving supplemental f olic/folinic acid and those on no therapy. This suggests that some mod ulation of the gene dosage effect may be possible.