Effects of the uricogenic agent, 2-ethylamino-1,3,4-thiadiazole in hypoxanthine-guanine phosphoribosyl transferase deficiency

Abstract

The effects of 2-ethylamino-1,3,4-thiadiazole have been assessed in two patients with a disorder of uric acid metabolism and cerebral function. Patients with this inborn error of metabolism have marked overproduction of purine, and absent activity of hypoxanthine, guanine phosphoribosyl transferase. It was found that this uricogenic thiadiazole increased further, the elevated concentrations of uric acid in blood and urine. Clinical reactions were dramatic, required vigorous therapy, and suggested that the investigation of this compound should not be undertaken lightly in patients with this disease. There was an increase in the cumulative conversion of 14C-labeled glycine into urinary uric acid. These observations indicate that the increased de novo purine synthesis of this condition is capable of further increase. They suggest the possibility that the overproduction of purine found in the disease and that which follows thiadiazoles, are both related to the role of guanine nucleotide in the feedback regulation of purine synthesis.