A 24-year-old man was admitted to our hospital because of gouty arthritis in the right instep and great toe. His initial attack of gout occurred at the age of 22. He had many cysts in both kidneys but not in the liver by study of abdominal CT and ultrasonography.
Two members of his family also suffered from polycystic kidney disease and gout. His serum urea was 12.7 mg/dl, creatinine 1.2 mg/dl, and uric acid 9.2 mg/dl on a regular diet. The mean daily urinary excretion of uric acid was 584 mg on a purine restricted diet. The uric acid clearance (C_UA) was 5.7% and fractional excretion of uric acid (C_UA/Ccr) was 5.3%, which suggested that reduced excretion of uric acid was the main cause of hyperuricemia in this patient. Urinary excretion of uric acid, hypoxanthine and xanthine were suppressed by oral administration of 3g pyrazinamide, similar to normal subjects. The activities of the enzyme HGPRT, APRT and PRPP synthetase in erythrocytes were normal. These results suggest that abnormal renal handling of uric acid is responsible for the onset of gout in this patient with polycystic kidney disease. This is the first report about familial occurrence of gout and polycystic kidney disease in Japan.

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We report a case of renal hypouricemia associated with acute renal failure. A 16-year-old boy was transferred to our hospital because of azotemia after exercise. He had been well until three days prior to admission, when he had developed nausea, anorexia, vomiting and oliguria following exercise. No loin pains or limb muscle tenderness developed, and macroscopic hematuria was not observed. On admission to the first hospital he was alert and had no edema and his blood pressure was within the normal range. Serum urea-N (BUN) and creatinine (s-Cr)levels were 47 and 6.1mg/dl, respectively. He was then transferred to our hospital for further examination, where, because no obvious causes of acute renal failure could be found, he received no aggressive therapy other than fluid replacement and bed rest. After admission urine output gradually increased from 600 to 3,000ml/day, and BUN and s-Cr levels decreased to within the normal range. Serum uric acid level was surprisingly low,3.8mg/dl, in spite of the elevated BUN and s-Cr levels, and then decreased to below 1.0 mg/dl after the recovery of renal function. Urine urate excretion was 770mg/day and urate clearance rate was as high as 76.4ml/min, and these rates, did not change after oral administration of benzbromarone and pyrazinamide. We did not find any depositions of urate in the tubular lumen of renal biopsy specimens. His father and two brothers also had hypouricemia and increased urate clearance.
We speculate that urine urate excretion could have been accelerated after exercise by the increased production of uric acid which resulted in acute urate nephropathy.

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We examined in the relation between acute arthritis and serum lipids in gouty patients. The concentrations of serum lipids ( T-chol, TG, PL, FC ) and apolipoproteins in serum were not changed by acute gouty arthritis.
However, the concentration of high density lipoprotein 2 cholesterol (HDL 2 -C) in serum was significantly higher on acute gouty arthritis. The alcohol consumption was increased before acute gouty arthritis. This may have caused the increased concentration of HDL 2 -C.
However, the relationship between acute gouty arthritis and the increased concentration of HDL 2 -C remains to be clarified.

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To investigate the erythrocyte purine metabolism in patients with chronic renal failure undergoing hemodialysis, erythrocyte purine nucleotides,2 - 3 DPG, the specific activities of some related enzymes and plasma purine nucleosides were measured together with plasma phosphate, and shunt blood pH before and after hemodialysis.
ATP, AMP and IMP levels were significantly elevated in erythrocytes of patients with chronic renal failure.
IMP level in erythrocytes decreased significantly after hemodialysis, while the levels of other nucleotides did not.
No relationships were noted between plasma phosphate concentration, shunt blood pH and levels of ATP and IMP in erythrocytes in patients with chronic renal failure.
2-3 DPG level in erythrocytes increased significantly after hemodialysis.
Red cell APRT activity was raised in patients with chronic renal failure, however the specific activities of HPRT, PRPP synthetase were not changed. Hemodialysis did not affect the specific activities of these enzymes.
The plasma inosine was reduced in patients with chronic renal failure, but plasma oxypurine was not changed.
These results suggested that intrinsic factor (s) of erythrocytes mainly affects the concentrations of ATP and AMP in erythrocytes and that extrinsic factor(s) mainly affects that of IMP in erythrocytes of patients with chronic renal failure.

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Purine nucleotide synthesis and the related enzyme activities during cell differentiation were examined in leukemic promyelocytes taken from a patient with acute promyelocytic leukemia (APL) being treated with retinol palmitate and in promyelocytic cell line HL- 60cells treated with retinol. In the patient with APL, treatment with retinol palmitate induced morphological and functional maturation of leukemic promyelocytes in vivo. Also in suspension cultures, retinol, the main metabolite of retinol palmitate in human plasma, induced morphological and functional maturation of HL- 60 cells. In these two types of cells, incorporation of hypoxanthine and glycine into the intracellular nucleotide pool decreased significantly. Both treated cells showed significantly increased hypoxanthine-guanine phosphoribosyltransferase activity, but decreased phosphoribosyl pyrophosphate synthetase activity. These findings suggest that the differentiated promyelocytic cells induced by retinol palmitate or retinol show a decrease in purine nucleotide synthesis and that the effect of conventional combination chemotherapy for APL, including 6 -mercaptopurine, may be reduced following treatment with retinol palmitate.

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Myogenic hyperuricemia is a novel type of secondary hyperuricemia that is caused by release of a large amount of purine metabolites from working skeletal muscles. Treatment of myogenic hyperuricemia in glycogenosis type V ( muscle phosphorylase deficiency ) or VII (muscle phosphofructokinase deficiency) is described.
1) Rest and restricted exercise: Bed rest gradually decreased blood uric acid, hypoxanthine and inosine in a patient with type VII glycogenosis.
2) Continuous glucose infusion: Bicycle-ergometer exercise caused an excessive increase in blood ammonia, hypoxanthine and uric acid in both patients with muscular glycogenosis type V and type VII. Intravenous infusion of glucose almost normalized this excessive increase in the patient with glycogenosis type V, while glucose infusion was ineffective in the patient with glycogenosis type VII. Since the glycolytic pathway is not impaired in glycogenosis type V, increased uptake and utilization of glucose following glucose infusion probably ameliorated excess purine degradation by improving muscular energy metabolism, and thus prevented the occurrence of myogenic hyperuricemia.
3) Allopurinol treatment: Allopurinol (300mg/day) was administered to the patient with glycogenosis type VII. The blood uric acid level was decreased from 15.0mg/dl to 5.1mg/dl after 2 weeks. Urinary uric acid excretion was also markedly decreased. On the other hand, urinary excretion of xanthine and hypoxanthine was increased by about 17 times and 4 times, respectively, but the total excreted purine level (sum of uric acid, xanthine and hypoxanthine)was decreased to about half. Blood and urinary purine levels are now satisfactorily controlled with 200mg/day of allopurinol.

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