Glycogen Storage Disease Type 0

The clinical presentation of this autosomal recessive genetic disease exhibits significant variations, having in mind the fact that both hyperglycemia and hypoglycemia can occur [1] [2]. Due to frequent feeding during infancy, patients are usually asymptomatic during this period of life, but as nighttime feeding gradually ceases, symptoms most commonly appear before breakfast, when insufficient glycogen stores and consequent hypoglycemia manifest as lethargy, nausea, vomiting, pallor and seizures in some cases [1] [3]. Even in the absence of overnight feeds, infants and children rarely suffer from severe fasting ketotic hypoglycemia because fatty acid oxidation is able to provide enough energy for the central nervous system and the brain until the mealtime, and many children are even asymptomatic for a prolonged period of time [4]. Long-term complications, such as growth impairment, osteopenia, hyperlipidemia and developmental delay, which are more prevalent among other GSDs, are rarely seen in GSD type 0 and the majority of children have a preserved cognitive function [3] [4]. On the other hand, postprandial hyperglycemia is not an uncommon finding in these patients, the reason being the inability of the liver to synthesize glycogen from glucose after meals, as hepatic synthase is the key enzyme in this process [2]. This finding may paradoxically point to diabetes mellitus as the underlying cause [3]. Although often accompanied by hyperlipidemia and hyperlactatemia, symptoms are rarely present and the diagnosis is often made incidentally in either case [2] [4].

Children suffering from glycogen storage disease type 0 are most frequently identified when laboratory testing reveals hypoglycemia during evaluation for illnesses, for eg. gastrointestinal or other conditions that impair proper food intake [4]. Nevertheless, a thorough patient history is a mandatory step during workup, and valuable information can be obtained regarding any changes in eating habits and the appearance of symptoms as a result of these changes. A thorough physical examination should follow, but a presumptive diagnosis is made by determining levels of glucose and ketones in blood and urine, while measurement of lactate levels is also a good initial method [4]. Administration of either glucose or galactose and subsequent measurements of blood lactate and lipids, as well as glucose, is a highly useful procedure to confirm aberrations in the glycolytic pathway [1]. Additional laboratory parameters that support GSD type 0 are elevated liver enzymes (alanine and aspartate aminotransferase, or ALT and AST, respectively) [4]. If valid clinical suspicion existed toward GSD type 0 in previous years, liver biopsy was considered to the gold standard in the diagnostic workup, but the introduction of non-invasive genetic tests to detect specific mutations have changed the role of biopsy when it comes to GSD type 0 [1] [4]. Identification of glycogen synthase 2 (GYS2) gene mutations on chromosome 12p12.2 is diagnostic for this GSD [1] [3].

1. Özen H. Glycogen storage diseases: New perspectives. World J Gastroenterol. 2007;13(18):2541-2553.
2. Soggia AP, Correa-Giannella ML, Fortes MAH, Luna AMC, Pereira MAA. A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0. BMC Medical Genetics. 2010;11:3.
3. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.
4. Weinstein DA, Correia CE, Saunders AC, Wolfsdorf JI. Hepatic Glycogen Synthase Deficiency: An Infrequently Recognized Cause of Ketotic Hypoglycemia. Mol Genet Metab. 2006;87(4):284-288.