Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The classical features of Type I glycogen storage disease (McKusick 23220) (GSD) are hepatomegaly, hypoglycaemia, and acidosis, enlargement of the kidneys and short stature. Glucose-6-phosphatase (EC 3.1.3.9) activity is defective not only in liver and kidney but also in small intestine (Field et al., 1965). In addition to the classical features, many patients suffer from episodes of diarrhoea (Fine et al., 1969). At the Hospital for Sick Children, Great Ormond Street, patients with the commoner forms of hepatic glycogen storage disease have episodes of diarrhoea or loose stools more commonly than was suspected. We have investigated small intestinal function in three patients with Type I GSD by both in vitro and in vivo techniques.
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PMID:Disordered intestinal function in glycogen storage disease. 22 44

Other investigators have shown that fructose infusion in normal man and rats acutely depletes hepatic ATP and P(i) and increases the rate of uric acid formation by the degradation of preformed nucleotides. We postulated that a similar mechanism of ATP depletion might be present in patients with glucose-6-phosphatase deficiency (GSD-I) as a result of ATP consumption during glycogenolysis and resulting excess glycolysis. The postulate was tested by measurement of: (a) hepatic content of ATP, glycogen, phosphorylated sugars, and phosphorylase activities before and after increasing glycolysis by glucagon infusion and (b) plasma urate levels and urate excretion before and after therapy designed to maintain blood glucose levels above 70 mg/dl and thus prevent excess glycogenolysis and glycolysis. Glucagon infusion in seven patients with GSD-I caused a decrease in hepatic ATP from 2.25 +/- 0.09 to 0.73 +/- 0.06 mumol/g liver (P <0.01), within 5 min, persisting in one patient to 20 min (1.3 mumol/g). Three patients with GSD other than GSD-I (controls), and 10 normal rats, showed no change in ATP levels after glucagon infusion. Glucagon caused an increase in hepatic phosphorylase activity from 163 +/- 21 to 311 +/- 17 mumol/min per g protein (P <0.01), and a decrease in glycogen content from 8.96 +/- 0.51 to 6.68 +/- 0.38% weight (P <0.01). Hepatic content of phosphorylated hexoses measured in two patients, showed the following mean increases in response to glucagon; glucose-6-phosphate (from 0.25 to 0.98 mumol/g liver), fructose-6-phosphate (from 0.17 to 0.45 mumol/g liver), and fructose-1,6-diphosphate (from 0.09 to 1.28 mumol/g) within 5 min. These changes, except for glucose-6-phosphate, returned toward preinfusion levels within 20 min. Treatment consisted of continuous intragastric feedings of a high glucose dietary mixture. Such treatment increased blood glucose from a mean level of 62 (range 28-96) to 86 (range 71-143) mg/dl (P <0.02), decreased plasma glucagon from a mean of 190 (range 171-208) to 56 (range 30-70) pg/ml (P <0.01), but caused no significant change in insulin levels. Urate output measured in three patients showed an initial increase, coinciding with a decrease in plasma lactate and triglyceride levels, then decreased to normal within 3 days after treatment. Normalization of urate excretion was associated with normalization of serum uric acid. We suggest that the maintenance of blood glucose levels above 70 mg/dl is effective in reducing serum urate levels and that transient and recurrent depletion of hepatic ATP due to glycogenolysis is contributory in the genesis of hyperuricemia in untreated patients with GSD-I.
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PMID:ATP depletion, a possible role in the pathogenesis of hyperuricemia in glycogen storage disease type I. 27 29

Type I glycogen storage disease (GSD-I) is due to the deficiency of glucose-6-phosphatase activity in the liver, kidney and intestine. Although kidney enlargement occurs in GSD-I, renal disease has not been considered a major problem until recently. In older patients (more than 20 years of age) whose GSD-I disease has been ineffectively treated, virtually all have disturbed renal function, manifested by persistent proteinuria; many also have hypertension, renal stones, altered creatinine clearance or a progressive renal insufficiency. Glomerular hyperfiltration is seen in the early stage of the renal dysfunction and can occur before proteinuria. In younger GSD-I patients, the hyperfiltration is usually the only renal abnormality found; and, in some patients, microalbuminuria develops before clinical proteinuria. The predominant underlying renal pathology is focal segmental glomerulosclerosis. Renal stones and/or nephrocalcinosis are also common findings. Amyloidosis and Fanconi-like syndrome can occur, but rarely. The risk factors for developing the glomerulosclerosis in GSD-I include hyperfiltration, hypertension, hyperlipidemia and hyperuricemia. Dietary therapy with cornstarch and/or nasogastric infusion of glucose, aimed at maintaining normoglycemia, corrects metabolic abnormalities and improves the proximal renal tubular function. Long-term trial will be needed to assess whether the dietary therapy may prevent the evolution or the progression of the renal disease.
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PMID:Type I glycogen storage disease: kidney involvement, pathogenesis and its treatment. 202 44

Liver glycogenosis (GSD) are hereditary in diseases caused by deficiencies of the three major enzymatic systems involved degradation of glycogen: glucose-6-phosphatase (GSD VI). The aims of this paper are, in a first part, to summarize the biological and physiological aspects of these disorders in order to propose an update diagnostic process, and, in a second part, to point out the clinical features and the possible evolution of such patients becoming adults, according to the French experience.
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PMID:[Hepatic glycogenoses. Introduction]. 316 6

Liver glycogenosis (GSD) are hereditary diseases caused by deficiencies of the three major enzymatic systems involved in glycogenolysis: glucose-6-phosphatase (GSD I), debranching enzyme (GSD III) and phosphorylase system (GSD VI). Biological and physiopathological aspects of these disorders are described. An up to date diagnostic process which includes measurement of glycogen and enzymatic activities, in the most appropriate tissue material, is proposed.
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PMID:[Biological and physiopathological aspects of hepatic glycogenoses]. 316 7

Patients with deficient activity of hepatic glucose-6-phosphatase (glycogen storage disease type I [GSD-I]) have fasting-induced hypoglycemia, lactic acidemia, hyperuricemia, hyperlipidemia, and a markedly increased capacity for ethanol elimination. The mechanism(s) responsible for the rapid ethanol elimination is not known but has been thought to be directly related to the enzyme defect. We postulated however, that the increased elimination of ethanol was an adaptive phenomenon that would revert toward normal with correction of other blood abnormalities by long-term maintenance of normal blood glucose concentration. Six patients were observed before treatment (group A), and four of the six were observed again 3 to 6 months after dietary treatment had normalized all blood abnormalities (group B). Patients received 16 ml/m2 absolute ethanol as a 5% solution in 0.9% sodium chloride over a 20-minute period. The rate of ethanol elimination was significantly greater (P less than 0.03) in group A than in group B (55.1 +/- 11.1 vs. 37.5 +/- 8.6 mg/dl/hr). Changes in lactate level after ethanol were also significant between the two groups (P less than 0.005). Group A showed a decrease from 9.4 +/- 0.5 to 6.4 +/- 0.4 mEq/L, whereas group B showed an increase in lactate level from 2.7 +/- 0.2 to 4.4 +/- 0.64 mEq/L. Ethanol induced no significant change in blood glucose concentration in group A, whereas there was a significant increase (P less than 0.03) in group B from 93 +/- 6 to 123 +/- 9 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid ethanol elimination in patients with type I glycogen storage disease is an adaptive change resulting from recurrent hypoglycemia. 345 5

Abnormal lipid transport is one of the more severe pathophysiological manifestations of glucose-6-phosphatase deficiency (glycogen storage disease, type I: GSD-I). To characterize further lipoprotein abnormalities in this inborn error of glycogen metabolism, we determined the levels of serum apolipoproteins (Apo) A-I, A-II, B, C-I, C-II, C-III, D, and E in 10 male and 12 female patients, 1-37 yr of age. Results showed that patients with GSD-I have a unique apolipoprotein profile characterized by normal or slightly decreased levels of ApoA-I and ApoA-II, reduced concentrations of ApoD, and significantly increased levels of ApoC-I and ApoC-II (p less than 0.01) and ApoB, ApoC-III, and ApoE (p less than 0.0001) in comparison with age- and sex-matched normolipidemic controls. However, there was some overlap of values in patients and controls for each of the lipid and apolipoprotein constituents with the exception of ApoC-III. This finding supported by the results of the logistic regression analysis showed that the concentration of ApoC-III is the best criterion for distinguishing patients with GSD-I from control subjects and the most characteristic feature of the deranged lipid transport system in this deficiency disease. It remains to be clarified, however, whether the ApoC-III concentrations in patients with GSD-I reflect the degree of other metabolic and clinical manifestations of this disease such as hyperlacticacidemia, hyperuricemia, and growth retardation.
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PMID:The serum apolipoprotein profile of patients with glucose-6-phosphatase deficiency. 385 88

1. GSD-I is described in a child with partial deficiency of hepatic glucose-6-phosphatase. 2. Growth retardation and hepatosplenomegaly were major clinical features. 3. Hyperlipidaemia, lactic acidaemia, hyperuricaemia and reduced uric acid clearance were major biochemical findings. 4. Although the glucose response to glucagon and galactose was impaired, there was a striking absence of hypoglycaemia which may be attributable to residual catalytic activity of the enzyme. 5. Preliminary studies of the crude liver enzyme showed it to have a normal pH inactivation profile and apparent Km with a reduced Vmax. 6. No evidence of increased PP-ribose-P availability in fresh liver tissue was detected. 7. Continuous glucose feeding resulted in accelerated growth without complete correction of lactic acidosis or hyperuricaemia. 8. GSD-I with partial deficiency of hepatic glucose-6-phosphatase should be considered in patients with gout or hyperuricaemia associated with hypertriglyceridaemia and lactic acidaemia even in the absence of hypoglycaemia.
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PMID:Clinical and enzymological studies in a child with type I glycogen storage disease associated with partial deficiency of hepatic glucose-6-phosphatase. 615 47

A girl presented with an important growth retardation, hepatomegaly, fasting hypoglycemia, lactic acidosis, increased serum cholesterol, triglycerides and uric acid, and increased liver glycogen (7.5%). There was no rise in blood glucose after IV galactose or fructose, but glucagon gave a delayed response. Type Ib glycogen storage disease was suggested by the low normal activity of glucose-6-phosphatase (G-6-Pase) which reached 1.8 units/g (normal, 2 to 10 units/g) and the normal activity of other glycogenolytic enzymes, measured in homogenates prepared in H2O (mean +/- S.E. in control subjects: 59% +/- 7; in type Ia GSD: 92% +/- 3). The activity of G-6-Pase measured as described above increased to 3.8 units/g of liver 1 year after PCS and 7.85 units/g of liver after 3 years. At that time, a simultaneous assay of the enzyme in a fresh, previously not frozen liver biopsy, homogenized in 0.25 M sucrose, revealed only about 29% of the activity of the same sample prepared in H2O (mean +/- S.E. in three controls: 95.8% +/- 8.9.
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PMID:Clinical and biochemical findings before and after portacaval shunt in a girl with type Ib glycogen storage disease. 625 80

Glycogen storage disease type I (GSD-I) is an inherited disorder that is due to a glucose-6-phosphatase (G6Pase) deficiency. There have been recent reports of hepatocellular tumors in adults with this disease. Hepatic adenoma is the most common tumor described but others, including hepatocellular carcinomas, hepatoblastomas, and focal nodular hyperplasia (FNH) have been reported. FNH of the liver is a rare benign lesion that has been reported in eight patients with GSD-I. Three of these eight patients, in addition to the patient in our study, had been treated with portacaval shunts. When these patients were compared with patients who had not received such treatment, it appeared that the portacaval shunts may have induced the development of FNH and may have been associated with earlier complications. FNH is a benign tumor that may coexist with adjacent fibrolamillar carcinomas and/or adenomas and requires careful follow-up.
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PMID:Type La glycogen storage disease with focal nodular hyperplasia in siblings. 757 55


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