Ketosis in Hepatic Glycogenosis

Fernandes, J.; Pikaar, N. A.

doi:10.1136/adc.47.251.41

Cited by 43 publications

(27 citation statements)

References 13 publications

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“…66 Blood lactate levels increase rapidly in GSD I as BG concentrations decrease to levels that normally trigger a counterregulatory response (<70 mg/dl or 4 mmol/l) and are markedly increased when BG levels decrease to <40-50 mg/dl or 2.2-2.8 mmol/l). Blood β-hydroxybutyrate levels increase only modestly in GSD I, 53,54 in contrast to marked hyperketonemia with fasting hypoglycemia characteristic of GSD 0, III, VI, and IX. 54 Other biochemical characteristics that help to distinguish between these disorders are elevated uric acid and lactate levels in GSD I, whereas these are typically normal in GSD III.…”

Section: Diagnostic Confirmation Differential Diagnosismentioning

confidence: 95%

“…Blood β-hydroxybutyrate levels increase only modestly in GSD I, 53,54 in contrast to marked hyperketonemia with fasting hypoglycemia characteristic of GSD 0, III, VI, and IX. 54 Other biochemical characteristics that help to distinguish between these disorders are elevated uric acid and lactate levels in GSD I, whereas these are typically normal in GSD III. At the time of diagnosis, serum concentration of hepatic transaminase (aspartate aminotransferase and alanine aminotransferase) are increased in GSD I and often return to normal or near-normal levels with appropriate treatment.…”

Section: Diagnostic Confirmation Differential Diagnosismentioning

confidence: 95%

“…53,54 Eruptive xanthomata may appear on the extensor surfaces of the extremities and on the buttocks. 55 These findings are becoming less common with increased awareness and earlier diagnosis.…”

Section: Genetics In Medicinementioning

confidence: 99%

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Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics

Kishnani

Austin

Abdenur

et al. 2014

Genetics in Medicine

358

554

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Section: Diagnostic Confirmation Differential Diagnosismentioning

confidence: 95%

Section: Diagnostic Confirmation Differential Diagnosismentioning

confidence: 95%

See 1 more Smart Citation

Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics

Kishnani

Austin

Abdenur

et al. 2014

Genetics in Medicine

358

554

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“…In untreated patients, high levels of lactate and pyruvate might prevent an appropriate fall in hepatic malonyl-CoA levels during fasting, and impair the oxidation of fatty acid delivered to the liver from adipose tissue. This would account for the massive accumulation of fat in the liver in untreated patients and the impairment in ketogenesis suggested by other workers (2,6,10) and our own data (Table 4). In treated patients, persistent elevations of lactate and pyruvate may support excessive hepatic fatty acid synthesis and triglyceride production.…”

Section: Discussionmentioning

confidence: 81%

Intragastric Feeding in Type I Glycogen Storage Disease: Factors Affecting the Control of Lactic Acidemia

1981

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“…In G6Pase-deficient children, however, this is impossible because there is no physiologic hyperketosis during fasting. Their fasting hypoglycemia is accompanied by hypoketosis (5) and hyperlactacidemia (6).…”

mentioning

confidence: 99%

Lactate as a Cerebral Metabolic Fuel for Glucose-6-Phosphatase Deficient Children

1984

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SummaryThe main substrates for brain energy metabolism were measured in blood samples taken from the carotid artery and the internal jugular bulb of four children with glycogen storage disease caused by deficiency of glucose-6-phosphatase. Multiple paired arterial and venous blood samples were analyzed for glucose, lactate, pyruvate, D-b-hydroxybutyrate, acetoacetate, glycerol and 02, and the arteriovenous differences of the concentrations were calculated. In the first three patients the substrates were measured in two successive conditions with lower and higher glucose-intake, respectively, inducing reciprocally higher and lower concentrations of blood lactate. In the fourth patient medium chain triglycerides were administered simultaneously with the glucose-containing gastric drip feeding.Lactate appeared to be taken up significantly. It consumed, if completely oxidized, between 40-50% of the total O2 uptake in most cases. Only once in one patient the uptake of lactate switched to its release, when the blood lactate level decreased to normal. D-B-hydroxybutyrate and acetoacetate arteriovenous (A-V) differences were small to negligible and these ketone bodies, therefore, did not contribute substantially to the brain's energy expenditure. Glycerol was not metabolized by the brain. Lactate thus appeared to be the second brain fuel next to glucose. It may protect the brain against fuel depletion in case of hypoglycemia. AbbreviationsA-V, arteriovenous AcAc, acetoacetate G6Pase, glucose-6-phosphatase GDF, gastric drip feeding MCT, medium chain triglycerides &OHB, Bhydroxybutyrate P, priming dose Some children with hepatic glycogenosis caused by G6Pase deficiency show a striking tolerance for hypoglycemia. Their brain function remains unimpaired even when the blood glucose concentration is very low. Remarkably, those of our patients who show the most pronounced metabolic disturbances and the highest lactate levels in the blood, appear to be the least suscep tible to clinical symptoms of hypoglycemia. On the other hand, patients with a less abnormal metabolic state and only moderately elevated lactate levels show cerebral symptoms as soon as their blood glucose drops to even moderately low levels. We, therefore, wondered whether in some patients, besides glucose, lactate might be utilized as an energy substrate by the brain and thus protect the child against the deleterious effects of glucose depletion. This would be opposite to the situation in normal children (18, 22, 24, 25, 26) and normal adults (4, 9, 23), in whom the brain releases lactate and consumes ketone bodies (P-OHB and AcAc) as soon as glucose, the preferential fuel, becomes insufficiently available. In G6Pase-deficient children, however, this is impossible because there is no physiologic hyperketosis during fasting. Their fasting hypoglycemia is accompanied by hypoketosis (5) and hyperlactacidemia (6).The ability to utilize lactate instead of ketone bodies would fierefore be a useful mechanism. If, indeed, substantial cerebral utilization of lactate we...

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Ketosis in Hepatic Glycogenosis

Cited by 43 publications

References 13 publications

Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics

Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics

Intragastric Feeding in Type I Glycogen Storage Disease: Factors Affecting the Control of Lactic Acidemia

Lactate as a Cerebral Metabolic Fuel for Glucose-6-Phosphatase Deficient Children

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