[Hepatic glycogen synthetase deficiency or glycogen storage disease-zero. Mild phenotype with partial enzymatic defect]

Abstract

Since the original description 26 years ago, of the hepatic glycogen synthetase deficiency, only one more case was reported in 1977. We present the studies carried out on an Argentine boy of Italian ancestry who at age 21 months, showed signs of hepatic deficiency with mild clinical symptoms which contrasted with a remarkable fatty liver degeneration. A totally atypic reaction to fructose overload (Table 1, Fig. 1) was the first key to the diagnosis. Glucose levels were not significantly modified by glucagon after 12-hours fasting, but it did increase the glycemia, with decrease of lactate and alanine 3 hours after-meal (Fig. 2a, b). The 24-hours metabolic profile showed fasting hypoglycemia, hyperketonemia, low alanine concentrations and mild lactatemia and hyperglycemia and a net post-prandial increase of lactate (Fig. 3). This profile when reduced to 14 hours, 12-fasting hours and 2-postprandial hours (Fig. 4), revealed similar alterations in an asymptomatic younger brother. The development of the investigation led to a second hepatic biopsy which confirmed hepatic steatosis and to an ultrastructural study, which showed subcellular alterations in the liver and also in muscle (Fig. 5). Moreover low content of hepatic glycogen was observed along with glycogen synthetase activity between 20-25% that of controls, being normal the enzyme activity in muscle and fibroblasts cultured from a skin biopsy (Table 2). The clinical pattern mainly without hypoglycemia, convulsions and/or mental retardation and a normal height and body mass development, allowed us to postulate that this Argentine report would be a mild variant of the disease formerly described and would be correlated with a partial deficiency of the hepatic glycogen synthetase.