J. Edwin Seegmiller

RECENT progress in the understanding of purine metabolism and uric acid disposition suggests a need to revise the traditional classification of hyperuricemia and gout. A rational classification based on uric acid production would provide the foundations for further genetic investigation and for a sound approach to the treatment of patients with gout.Hyperuricemia is difficult to define. The serum urate concentration is not distributed normally in the population but is slightly skewed toward higher values. A functional and useful definition is based on the physicochemical saturation of serum with urate, which at 37°C is about 7.0 mg per 100 ml. . . .

In patients with cystinosis, the concentration of free cystine in leukocytes was 80 times greater than normal, and six times the normal content for their parents. This is the first demonstration of an abnormality in heterozygotes for this rare inherited disease of childhood. Three-quarters of the cystine was recovered in the granular fraction of cystinotic leukocytes.

SINCE its clinical introduction in 1964, allopurinol (4-hydroxypyrazolo-[3,4-d]-pyrimidine) has been increasingly used for the treatment of hyperuricemia of gout,1 , 2 many neoplastic diseases and other metabolic disorders. Allopurinol and its principal metabolic product, oxipurinol (alloxanthine, oxoallopurinol), inhibit the enzyme, xanthine oxidase, that normally converts hypoxanthine to xanthine, and xanthine to uric acid. The concentration of these oxypurine precursors of uric acid in blood and urine thus increases in patients treated with allopurinol.Although the formation of urinary xanthine stones has been anticipated as a possible complication of allopurinol therapy, to date this occurrence has not been documented in the clinical use . . .