Uric Acid Production in Gout

Seegmiller, J. Edwin; Grayzel, Arthur I.; Laster, Leonard; Liddle, Lois

doi:10.1172/jci104360

Cited by 207 publications

(73 citation statements)

References 22 publications

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“…As shown in Table 2, only the index patient of family 1 showed an excessive production of uric acid (>600 mg/day) (10). However, on the second day of a diet essentially free offructose as well as of purines, the 24-hr excretion of uric acid had decreased to 623 mg and the ratio of uric acid to creatinine had also decreased from 0.54 to 0.43.…”

Section: Resultsmentioning

confidence: 96%

“…Creatinine was measured in urine by a modified kinetic Jaffe method (kit 4040-7042), and urate was measured in urine and plasma by a modified phosphotungstate method (kit 4170-4172), using a Parallel analyzer obtained from American Monitor (Burgess Hill, Sussex, U.K.). The lowfructose diet consisted of avoiding all fruit, all foods containing sucrose, and those vegetables containing significant amounts of fructose (9) along with a constant diet very low in purine content with dairy products providing the major source of protein (10).…”

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confidence: 99%

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Fructose-induced aberration of metabolism in familial gout identified by 31P magnetic resonance spectroscopy.

Seegmiller

Dixon

Kemp

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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The hyperuricemia responsible for the devel-.pment of gouty arthritis results from a wide range of environmental factors and underlying genetically determined aberrations of metabolism. 31p magnetic resonance spectroscopy studies of children with hereditary fructose intolerance revealed a readily detectable rise in phosphomonoesters with a marked fall in inorganic phosphate in their liver in vivo and a rise in serum urate in response to very low doses of oral fructose. Parents and some family members heterozygous for this enzyme deficiency showed a similar pattern when given a substantially larger dose of fructose. Three of the nine heterozygotes thus identified also had clinical gout, suggesting the possibility of this defect being a fairly common cause of gout.In the present study this same noninvasive technology was used to identify the same spectral pattern in 2 of the 11 families studied with hereditary gout. In one family, the index patient's three brothers and his mother all showed the fructose-induced Hereditary fructose intolerance is known to be associated with hyperuricemia although the major clinical manifestations, as the name implies, have to do with severe or even fatal adverse reactions to ingested fructose as a result of a recessively inherited defect of aldolase B, resulting in loss of its capacity to split fructose 1-phosphate (3). A publication (4) has claimed the putative identification of the abnormal gene for fructose intolerance. By using conventional biochemical tests, only intestinal biopsy has provided a method for the detection of heterozygotes (5). However, heterozygotes were readily identified noninvasively in studies of affected and unaffected family members by using in vivo 31p magnetic resonance (MR) spectroscopy of the liver before and after an oral fructose load (6). The homozygous affected children showed a marked increase in the phosphomonoester (PME) peak and a substantial decrease in the peak for inorganic phosphate (Pi) in response to very low doses of oral fructose.The parents, as expected for obligate heterozygotes, along with some of the siblings and other clinically unaffected family members showed a similar pattern in response to much larger doses of oral fructose (6). Of special interest was the finding of clinical gout in three of the nine heterozygotes identified by MR spectroscopy (6). The calculated incidence of the heterozygote in the European population [1/80 in Switzerland (3) to 1/250 in Great Britain (6)] is of sufficient frequency to account for a significant portion of gout patients. Infusion of fructose increases serum urate in normal children, in children with hereditary fructose intolerance (7), and in gouty and nongouty adult volunteers (7,8).In the present study, MR spectroscopy was used to monitor the changes induced by a 50-g load of oral fructose in the Pi and PME peaks in the liver of a group of 11 volunteers with familial gout. In addition, an indication of the magnitude of endogenous uric acid production ofeach patient was obtained and t...

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Section: Resultsmentioning

confidence: 96%

mentioning

confidence: 99%

Fructose-induced aberration of metabolism in familial gout identified by 31P magnetic resonance spectroscopy.

Seegmiller

Dixon

Kemp

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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show abstract

“…At the peak, the specific activity in the patient approximated 4 times that of controls. In experiments of this type, it has not been possible to distinguish adults with gout from control adults [13]. Therefore, the cumulative recovery of the isotope of glycine in urinary uric acid has been employed to characterize those in whom gout is clearly associated wit5 overproduction of uric acid.…”

Section: Results Hfetabolic Investigation Q F P a T I~n T D Bmentioning

confidence: 99%

Genetics of an X-Linked Disorder of Uric Acid Metabolism and Cerebral Function

et al. 1967

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“…In addition, IR (KBr) and mass [mlz: 167 (M+, C s H s N s 0 2 )] spectra were identical with those of an authentic sample as shown in Figs. 4 and 5.…”

Section: Histopathological Findingsmentioning

confidence: 99%