Studies in liver glycogen disease: Effects of glucagon and other agents on metabolic pattern and clinical status

Clinical and biochemical studies in nine children with liver glycogen disease are reported. Major discrepancies were observed between in vitro determinations of hepatic enzyme activity and clinical findings in the subjects under study. In particular, there was no correlation between the levels of glucose-6-phosphatase measured in biopsy specimens of liver and the degree of fasting hypoglycemia. It is concluded that none of the enzymatic defects so far described account satisfactorily for the manifestations of liver glycogen disease. In most of the patients studied, hyperlacticemia was a prominent feature of the fasting state. Feeding or glucose infusion resulted in decrease of the blood lactate levels. Injection of glucagon appeared to induce hepatic glycogenolysis, but with lactate as the principal end product instead of glucose. Decrease in liver size was observed in these patients during glucagon infusion. Two patients behaved differently, however; lactate levels in their blood were normal during fasting, and administration of glucagon did not result in release of either glucose or lactate by the liver. In five of six patients so studied, the administration of glucagon after feedings resulted in sustained elevation of blood glucose levels, with an initial increase, then a sharp decrease in lactate levels in blood. After this, concentrations of lactate were maintained near normal levels for several hours. When long-acting glucagon was administered, the effects appeared to persist up to eight hours. Explanations are suggested for the fasting hyperlacticemia, acidosis and ketosis of liver glycogen disease and for the characteristic hyperlipemia and fat accumulation in the liver. Postprandial injections of glucagon may be useful in the management of some children with liver glycogen disease.