Hyperuricemia in Glycogen-Storage Disease Type 1

Abstract

THE ASSOCIATION of hyperuricemia with glycogen-storage disease (GSD) type 1 or von Gierke's disease has been described in 20 patients.1 In some of these patients gouty arthropathy and nephropathy have occurred.2-4 The mechanism responsible for hyperuricemia has not been delineated, but is thought to result from altered renal tubular function.5 Normally, 90%-95% of the uric acid which is filtered at the glomeruli is reabsorbed by the proximal renal tubules. The major portion which appears in the urine seems to be secreted by the distal renal tubules.6 It has been hypothesized that the hyperlacticacidemia which these patients manifest either enhances renal tubular reabsorption or inhibits renal tubular secretion of uric acid, thereby decreasing uric acid clearance (Cur) and producing hyperuricemia.3The purpose of this study was to determine the effect of lactic acid and glucose in the development of hyperuricemia in patients with GSD type 1. MaterialsNine patients with clinical findings of GSD type 1 who met the following biochemical criteria were studied for evidence of hyperuricemia : no response to glucagon HC1 (0.1 mg/kg subcutaneous) or ga¬ lactose (1.75 gm/kg I.V.), elevated serum lactic acid levels, and absence of glucose-1-phosphatase in liver.Renal clearance studies were performed on the three oldest hyperuricemia patients, D.T., L.I., and U.T. previously had clinical manifestations of uric acid nephropathy, but at the time clearance studies were performed, gross meas¬ urements of renal function were normal : urinalysis, blood urea nitrogen (BUN), intravenous pyelogram (IVP), and inulin clearance.Procedures.-All urine samples were analyzed for inulin, uric acid, and pH value. All blood sam¬ ples were analyzed for inulin, uric acid, CO2, glu¬ cose, and lactic acid; pH was measured in random blood samples.Three consecutive half-hour urine collections were obtained during each study period, after a one-or two-hour equilibration period. Blood specimens were obtained midway between each urine collection period.1. Control Studies.-After an overnight fast, the bladder was emptied by means of an indwelling catheter. A priming dose of inulin was then admin¬ istered intravenously followed by an intravenous infusion of a sustaining dose of inulin in normal saline delivered at a constant rate of 300 ml/hour. 2. Glucose Infusion.-The sustaining dose of inulin in 10% glucose was infused at a rate of 300 ml/hour after control periods.3. Lactate Infusion (D.T. and U.T.).-A 10% glucose solution was infused overnight at a rate of 75 ml/hour for seven hours. The infusion of a prim¬ ing dose of inulin in 10% glucose delivered at a rate of 300 ml/hour immediately followed. Prior to the inulin infusion the bladder was emptied by means of an indwelling catheter.Glucose infusion was discontinued after 2}/2 hours and lactate (125 ml .3 M sodium lactate plus 175 ml normal saline (D.T.), 150 ml 0.3 M sodium lactate plus 150 ml normal saline (U.T.), together with the sustaining dose of inulin was infused at a rate of 300 ml/hour. Met...

Growth in Glycogen-Storage Disease Type 1

“…Renal func¬ tion was normal in the four patients studied. 4 There was no evidence of abnormal endocrine function in our patients. Thy¬ roid function was normal as evidenced by normal PBI values and the lack of clinical findings of hypothyroidism.…”

Hyperuricemia in glycogen storage disease type I. Contributions by hypoglycemia and hyperglucagonemia to increased urate production.

“…Hyperuricemia and gout occur frequently in glucose-6-phosphatase deficiency (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(24)(25)(26). The hyperuricemia results from both a decreased renal clearance of urate secondary to lactic acidemia (1,4,5) and ketonemia (2) and increased production of uric acid (2,3,6,7).…”

“…The hyperuricemia results from both a decreased renal clearance of urate secondary to lactic acidemia (1,4,5) and ketonemia (2) and increased production of uric acid (2,3,6,7). Decreased renal clearance of urate was evident in the three patients studied (Table I).…”

ATP Depletion, a Possible Role in the Pathogenesis of Hyperuricemia in Glycogen Storage Disease Type I

“…Second, glucagon infusion should activate hepatic phosphorylase causing hydrolysis of a sufficient quantity of glycogen to give rise to large amounts of phos- FIGURE 4 Hepatic ATP levels in rats after injection of either glucagon (50 gg/kg) or diluent into the inferior vena cava.…”

“…The correction of hyperlacticacidemia could therefore contribute to the increased excretion of urate during the early phase of treatment (3, 4), although Fine et al. have shown that glucose infusion increases renal urate excretion before lactate levels fall (35). Normalization of serum urate, followed by an overall decrease in uric acid excretion after 2 wk of treatment suggests that urate production was decreased by treatment.…”