Glycogen storage disease (GSD) type 0, also known as hepatic glycogen synthase deficiency, is characterized by reduced capacity of the liver to store glycogen due to the absence of an enzyme responsible for the conversion of glucose to glycogen in the liver. Both hypoglycemia and hyperglycemia can induce symptoms and the diagnosis is made by a thorough laboratory workup, genetic studies, and biopsy of the liver.
The clinical presentation of this autosomal recessive genetic disease exhibits significant variations, having in mind the fact that both hyperglycemia and hypoglycemia can occur  . 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  . 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 . 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  . 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 . This finding may paradoxically point to diabetes mellitus as the underlying cause . Although often accompanied by hyperlipidemia and hyperlactatemia, symptoms are rarely present and the diagnosis is often made incidentally in either case  .
Entire Body System
Decrease in Height
[…] body height Small stature [ more ] 0004322 Percent of people who have these symptoms is not available through HPO Autosomal recessive inheritance 0000007 Fasting hypoglycemia Low blood sugar when fasting 0003162 Increased serum lactate 0002151 Neonatal [rarediseases.info.nih.gov]
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 . 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 . 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 . Additional laboratory parameters that support GSD type 0 are elevated liver enzymes (alanine and aspartate aminotransferase, or ALT and AST, respectively) . 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  . Identification of glycogen synthase 2 (GYS2) gene mutations on chromosome 12p12.2 is diagnostic for this GSD  .
The diagnosis of GSD0 should be considered in a child with ketotic fasting hypoglycemia with postprandial hyperglycemia but without hepatomegaly. [ncbi.nlm.nih.gov]
Mortality/Morbidity The major morbidity is a risk of fasting hypoglycemia, which can vary in severity and frequency. [emedicine.com]
In patients with glycogen-storage disease type 0, fasting hypoglycemia occurs within a few hours after a meal because of the limited stores of hepatic glycogen and inadequate gluconeogenesis to maintain normoglycemia. [en.wikipedia.org]
Patients present with morning fatigue and fasting hypoglycemia (without hepatomegaly) associated with hyperketonemia but without hyperalaninemia or hyperlactacidemia. [orpha.net]
After meals, major hyperglycemia associated with lactate and alanine increase and hyperlipidemia is observed. Etiology Glycogen synthetase deficiency is caused by mutations in the GYS2 gene (12p12.2). [orpha.net]
The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]
Please consult your own licensed physician regarding diagnosis and treatment of any medical condition! Please see also our disclaimer. This site complies with the HONcode standard for health information: verify here. Database updated 2019-03-22. [diseasesdatabase.com]
If you have questions about which treatment is right for you, talk to your healthcare professional. [rarediseases.info.nih.gov]
However, the focus of the book remains clinical, describing symptoms and signs at presentation, how to come to a diagnosis and methods for treatment. As with the previous edition, the book can be used in two main ways. [books.google.com]
Prognosis Prognosis is favorable when the disease is correctly managed. The documents contained in this web site are presented for information purposes only. [orpha.net]
Prognosis depends on the age of onset on symptoms with a better prognosis being associated with later onset disease. It has an autosomal recessive inheritance pattern. [en.wikipedia.org]
Prognosis : mostly death by age 4, due to cirrhosis and portal hypertension. Type V: McArdle's disease See the separate article on McArdle's Glycogen Storage Disease. [patient.info]
Identification of a pathogenic variant may assist with prognosis, clinical management, familial screening, and genetic counseling. [mayomedicallaboratories.com]
Etiology Glycogen synthetase deficiency is caused by mutations in the GYS2 gene (12p12.2). [orpha.net]
Etiology germline mutation in the glycogen synthase 2 Physiopathology Glucose use is strictly controlled and abnormal glucose handling is associated with some human diseases, such as glycogen storage diseases and diabetes. [humpath.com]
Development of guidelines to allow for systematic review and microarray studies are needed to better delineate the etiology of the HCC in patients with GSD-III. There are usually periportal fibrosis, and sometimes progress to micronodular cirrhosis. [wjgnet.com]
Summary Epidemiology It is an extremely rare disease; about 20 cases have been reported in the literature so far. Clinical description It commonly appears in infancy or in early childhood. [orpha.net]
The 4th edition includes an entirely new section on pediatric obesity: epidemiology, pathophysiology, assessment and treatment. It includes new chapters on celiac disease, food allergies and iron. [books.google.com]
Epidemiology Frequency International The overall frequency of glycogen-storage disease is approximately 1 case per 20,000-25,000 people. Glycogen-storage disease type 0 is a rare form, representing less than 1% of all cases. [emedicine.com]
Epidemiology [ edit ] The overall frequency of glycogen-storage disease is approximately 1 case per 20,000–25,000 people. Glycogen-storage disease type 0 is a rare form, representing less than 1% of all cases. [en.wikipedia.org]
Among the pediatric texts available, none deals with the physiologic or pathophysiologic basis of nutrition in pediatric health and disease in children of all ages. [books.google.com]
Pathophysiology In the early stages of fasting, the liver provides a steady source of glucose from glycogen breakdown (or glycogenolysis). [emedicine.com]
[…] glycogen-storage disease type 0 do not demonstrate correlations between genotype and phenotype.  A different gene (GYS1, 138570) encodes muscle glycogen synthetase, which has normal activity in patients with glycogen-storage disease type 0A.  Pathophysiology [en.wikipedia.org]
[…] glycogen storage disease including the pathophysiology of hepatic adenomas, hepatocellular carcinoma, nephrolithiasis, anemia, and focal segmental glomerulosclerosis Investigation of new medical treatments for glycogen storage disease [connecticutchildrens.org]
The goal of treatment for Type 0 Glycogen Storage Disease is to prevent low blood sugar (hypoglycemia) by avoiding fasting. Frequent meals and snacks can be given every 3-4 hours during the day. [agsdus.org]
Mutations in the GYS1 or GYS2 gene lead to a lack of functional glycogen synthase, which prevents the production of glycogen from glucose. Mutations that cause GSD 0 result in a complete absence of glycogen in either liver or muscle cells. [ghr.nlm.nih.gov]
The Lipid Research Clinics Coronary Primary Prevention Trial Results, II: the relationship of reduction in incidence of coronary heart disease to cholesterol lowering. [books.google.es]
For some children, eating several small meals rich in sugars and starches every day helps prevent blood sugar levels from dropping. Cornstarch. [childrenliverindia.org]
Prevention There is no way to prevent GSDs. However, early treatment can help control the disease once a person has it. If you have a GSD or a family history of the disorder, you may want to consult a genetic counselor. [wmhs.com]
- Özen H. Glycogen storage diseases: New perspectives. World J Gastroenterol. 2007;13(18):2541-2553.
- 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.
- 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.
- 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.