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Glycogen Storage Disease Type 0

Glycogen Synthase Deficiency Disease

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.


Presentation

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].

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]
Excitement
  • It is our hope that the 2nd Edition will open new avenues and vistas for our readers and that they will share with us the interest, excitement and passion of the research into all these challenging disorders.[books.google.com]

Workup

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].

Fasting Hypoglycemia
  • Biochemical evaluation as well as direct sequencing of exons and exon-intron boundary regions of the GYS2 gene were performed in a patient presenting fasting hypoglycemia and postprandial hyperglycemia and her parents.[ncbi.nlm.nih.gov]
  • 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]
  • Glycogen storage disease type 0 (GSD-0) is a rare form of fasting hypoglycemia presenting in infancy or early childhood and accompanied by high blood ketones and low alanine and lactate concentrations.[ncbi.nlm.nih.gov]
  • Patients present with morning fatigue and fasting hypoglycemia (without hepatomegaly) associated with hyperketonemia but without hyperalaninemia or hyperlactacidemia.[orpha.net]
  • Mortality/Morbidity The major morbidity is a risk of fasting hypoglycemia, which can vary in severity and frequency.[emedicine.medscape.com]

Treatment

  • What ́s new - Additional chapter focusing on inborn errors affecting adults, particularly the late neurological presentations - Numerous updates on diagnostic procedures and treatment - Newly discovered disorders.[books.google.com]
  • Last updated: 2/23/2011 The resources below provide information about treatment options for this condition. 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]
  • 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]
  • Treatment Regular snacks, cornstarch to reduce overnight hypoglycemia. Outlook Good with adherence to recommended feeding.[agsd.org.uk]

Prognosis

  • 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 : 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]
  • The combined dietary and G-CSF therapies significantly alleviate the metabolic and myeloid abnormalities of GSD-Ib patients and greatly improve their prognosis.[wjgnet.com]

Etiology

  • 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]

Epidemiology

  • 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]
  • 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]
  • Epidemiology [ edit ] Frequency (International) [ 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]
  • 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.medscape.com]
  • The GSD classification is based on the enzyme deficiency and the affected tissue. [ 3 ] Epidemiology The overall GSD incidence is estimated at 1 case per 20,000-43,000 live births. [ 4 ] Type I is the most common (25% of all GSDs).[patient.info]
Sex distribution
Age distribution

Pathophysiology

  • 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]
  • […] glycogen-storage disease type 0 do not demonstrate correlations between genotype and phenotype. [3] A different gene (GYS1, 138570) encodes muscle glycogen synthetase, which has normal activity in patients with glycogen-storage disease type 0A. [2] 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]
  • Pathophysiology In the early stages of fasting, the liver provides a steady source of glucose from glycogen breakdown (or glycogenolysis).[emedicine.medscape.com]
  • Adrogue, Metabolic acidosis: pathophysiology, diagnosis and management. J Nephrol. 19 Suppl. 9 , S62 (2006) M. Kosch et al., Störungen des Säure-Basen-HaushaltsRationale Diagnostik und ökonomische Therapie. Dtsch. Ärzteblatt 102 , B 1603 (2005) Y.S.[charite.de]

Prevention

  • Treatment aims to prevent hypoglycemia by taking snacks every 3-4 hours. Uncooked cornstarch can act as a 'slow release' form of glucose and may prevent hypoglycemia overnight.[agsd.org.uk]
  • 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]
  • 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]
  • 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]
  • For some children, eating several small meals rich in sugars and starches every day helps prevent blood sugar levels from dropping. Cornstarch .[childrenliverindia.org]

References

Article

  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.

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Last updated: 2018-06-21 18:28