Hepatic glycogen synthase deficiency: an infrequently recognized cause of ketotic hypoglycemia

Abstract

The glycogen storage diseases comprise several inherited diseases caused by abnormalities of enzymes that regulate the synthesis or degradation of glycogen. In contrast to the classic hepatic glycogen storage diseases that are characterized by fasting hypoglycemia and hepatomegaly, the liver is not enlarged in GSD0. Patients with GSD0 typically have fasting ketotic hypoglycemia without prominent muscle symptoms. Most children are cognitively and developmentally normal. Short stature and osteopenia are common features, but other long-term complications, common in other types of GSD, have not been reported in GSD0. Until recently, the definitive diagnosis of GSD0 depended on the demonstration of decreased hepatic glycogen on a liver biopsy. The need for an invasive procedure may be one reason that this condition has been infrequently diagnosed. Mutation analysis of the GYS2 gene (12p12.2) is a non-invasive method for making this diagnosis in patients suspected to have this disorder. This mini-review discusses the pathophysiology of this disorder, use of mutation analysis to diagnose GSD0, and the clinical characteristics of all reported cases of GSD0.

Figure 1

Schematic representation of biochemical pathways affected in glycogen storage disease type 0

Figure 2

Schematic representation of GYS2 gene with mutations that have been found in patients with GSD0. The gene has 16 exons (represented by the lines), and the arrowheads point to the location of the mutation.

Figure 3

Fasting and feeding study in a subject with mutation proven glycogen storage disease type 0 demonstrating the classic biochemical pattern of fasting hypoglycemia alternating with postprandial hyperlactatemia and hyperglycemia. Symbols represent times of events during the fasting and feeding study: (*) glucagon administration (0.3 mg/kg); (**) mixed meal/breakfast; and (***) mixed meal/lunch. Adapted from [9], and used with permission from Elsevier Publishers and the Journal of Pediatrics.