URATE KINETICS IN HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE DEFICIENCY - THEIR SIGNIFICANCE FOR UNDERSTANDING OF GOUT

Abstract

Urate production (miscible urate pool and turnover, daily production, glycine incorporation into urate) and urate excretion (24 h urinary urate excretion on a purine free diet, renal clearances of urate and creatinine, per-cent renal excretion of labeled urate, extra-renal elimination of urate) were measured in members of 5 families who demonstrated varying degrees of deficiency of the X-linked condition hypoxanthine-guanine phosphoribosyltransferase deficiency. The hemizygous males, all of whom eventually developed symptoms, showed consistent overproduction of urate with a renal excretion of urate that varied from moderately to considerably increased. The 9 heterozygotes, of whom 7 were asymptomatic, also showed abnormalities of urate production, although all but 2 had normal serum urate concentrations. The 1 heterozygote who developed gouty arthritis had the lowest renal excretory capacity for urate; the 1 heterozygote who developed an episode of renal colic had the highest urate clearance. In the heterozygotes with normal serum urate concentrations, the increased urate production was balanced by the renal excretion of urate. This demonstrates the importance of the relation between urate production and urate excretion in determining the clinical expression of abnormal urate metabolism.