Urate kinetics in hypoxanthine-guanine phosphoribosyltransferase deficiency: their significance for the understanding of gout.
Urate production (miscible urate pool and turnover, daily production, glycine incorporation into urate) and urate excretion (24 hour urinary urate excretion on a purine free diet, renal clearances of urate and creatinine, per cent renal excretion of labelled urate, extra-renal elimination of urate) were measured in members of five families who demonstrated varying degrees of deficiency of the X-linked condition hypoxanthine-guanine phosphoribosyltransferase (HGPRT) 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 nine heterozygotes, of whom seven were asymptomatic, also showed abnormalities of urate production, although all but two had normal serum urate concentrations. The one heterozygote who had developed gouty arthritis had the lowest renal excretory capacity for urate, whereas the one heterozygote who had developed an episode of renal colic had the highest urate clearance. In the heterozygotes with normal serum urate concentrations, the increase urate production was balanced by the renal excretion of urate. This demonstrates the importance of the relation between urate. This demonstrates the importance of the relation-between urate production and urate excretion in determining the clinical expression of abnormal urate metabolism.
D000293:Adolescent; D000328:Adult; D001168:Arthritis / Q000150:complications; D002986:Clinical Trials as Topic; D003404:Creatinine / Q000378:metabolism; D005260:Female; D008040:Genetic Linkage; D005998:Glycine / Q000378:metabolism; D006073:Gout / Q000150:complications / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency*; D007926:Lesch-Nyhan Syndrome / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D014527:Uric Acid / Q000097:blood / Q000378:metabolism* / Q000652:urine
D014527:Uric Acid; D003404:Creatinine; D007041:Hypoxanthine Phosphoribosyltransferase; D005998:Glycine