Glycogen Storage Disease Type I

Glycogen Storage Disease Type I

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Glycogen Storage Disease Type I is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • GSDI
  • glucose-6-phosphatase deficiency
  • glycogenosis type I
  • Von Gierke disease

Disorder Subdivisions

  • glycogen storage disease type IA
  • glycogen storage disease type IB

General Discussion

Glycogen storage diseases are a group of disorders in which stored glycogen cannot be metabolized into glucose to supply energy for the body. Type I glycogen storage disease is inherited as an autosomal recessive genetic disorder. Glycogen storage disease type I (GSDI) is characterized by accumulation of glycogen and fat in the liver and kidneys that can result in an enlarged liver and kidneys and growth retardation leading to short stature. GSDI is associated with abnormalities in the G6PC gene (GSDIA) or SLC37A4 gene (GSDIB) that result in enzyme deficiencies that cause excess amounts of glycogen accumulation in the body tissues and low levels of glucose in the blood. This enzyme deficiency also results in derangement of other important metabolites in the body thus causing imbalance or excessive accumulation of these metabolites.

Symptoms

The primary symptom of GSDI in infancy is a low blood sugar level (hypoglycemia). Symptoms of GSDI usually begin at three to four months of age and include enlargement of the liver (hepatomegaly), kidney (nephromegaly), elevated levels of lactate, uric acid and lipids (both total lipids and triglycerides), and seizures caused by repeated episodes of hypoglycemia. Continued low blood sugar can lead to delayed growth and development and muscle weakness.



High lipid levels can lead to the formation of fatty skin growths called xanthomas. Other conditions that can be associated with untreated GSD1 include osteoporosis, delayed puberty, gout (arthritis caused by accumulation of uric acid), kidney disease, pulmonary hypertension (high blood pressure in the arteries that supply the lungs), hepatic adenoma (benign liver tumors), polycystic ovaries in females, an inflammation of the pancreas (pancreatitis) and brain damage. Early diagnosis and effective treatment can result in normal growth and puberty and many affected individuals live into adulthood and enjoy normal life activities. Many female patients have had successful pregnancies.

Causes

Type I glycogen storage disease is associated with abnormalities in two genes. Mutations in the G6PC gene result in a deficiency in the glucose-6-phosphatase (G6Pase) enzyme and account for approximately 80% of GSDI. This type of GSDI is termed glycogen storage disease type Ia. Mutations in the SLC37A4 gene result in a deficiency in the glucose-6-phosphatase translocase enzyme (transporter deficiency) and account for approximately 20% of GSDI. This type of GSDI is termed glycogen storage disease type Ib. These enzyme deficiencies cause excess amounts of glycogen to be stored in the body tissues. In general GSD type Ib patients have similar clinical manifestations as type Ia patients but in addition, the white blood cells (neutrophils) are low in number and do not function normally (neutropenia). This can result in frequent infections and mouth ulcers.



Type I glycogen storage disease is inherited as an autosomal recessive genetic disorder. Recessive genetic disorders occur when an individual happens to inherit two copies of the same abnormal gene for the same trait/disease from each parent. If an individual receives one normal copy of the gene (allele) and one abnormal/defective copy of gene (allele) for the disease, the person will be a carrier for the disease, but usually will not show symptoms. Thus most parents of the person affected with GSD type I are unaffected carriers if the disease gene. The risk for two carrier parents having a child and passing the same defective gene to the new baby, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for GSDI is 25%. The risk is being affected is the same for males and females



Usually, all individuals are thought to carry at least 2-7abnormal alleles/genes (single abnormal gene copy) in their body. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases their risk to have children with a recessive genetic disorder.

Affected Populations

Type I glycogen storage disease occurs in approximately 1 in 100,000 births. The prevalence of GSDI in Ashkenazi Jews is approximately 1 in 20,000. This condition affects males and females in equal numbers in any given population group.

Standard Therapies

Diagnosis

GSD type I is diagnosed by laboratory tests that indicate abnormal levels of glucose, lactate, uric acid, triglycerides and cholesterol. Molecular genetic testing for the G6PC and SLC37A4 genes is available to confirm a diagnosis. Molecular genetic testing can also be used for carrier testing and prenatal diagnosis. Liver biopsy can also be used to prove specific enzyme deficiency.



Treatment

GSDI is treated with a special diet in order to maintain normal glucose levels, prevent hypoglycemia and maximize growth and development. Frequent small servings of carbohydrates during the day must be maintained throughout life. Calcium, vitamin D and iron supplements may be recommended. Feeding of uncooked cornstarch is used to improve blood levels of glucose. Allopurinol, a drug capable of reducing the level of uric acid in the blood, may be useful to control the symptoms of gout-like arthritis during the adolescent years. Medications may be prescribed to lower lipid levels and prevent and/or treat kidney disease. Human granulocyte colony stimulating factor (GCSF) may be used to treat recurrent infections in type Ib patients. Liver tumors can be treated with surgery or a procedure in which current is used to heat and eliminate the tumor (radiofrequency ablation). Kidney and/or liver transplantation are sometimes considered if other therapies are unsuccessful or where liver adenomas keep growing.



Individuals with GSDI should be monitored at least annually with kidney and liver ultrasound and routine blood work specifically used for monitoring GSD patients.



Genetic counseling is recommended for affected individuals and their families.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Chen YT, Bali DS. Prenatal Diagnosis of Disorders of Carbohydrate Metabolism. In: Milunsky A, Milunsky J, eds. Genetic disorders and the fetus - diagnosis, prevention, and treatment. 6th ed. West Sussex, UK: Wiley-Blackwell; 2009.



Chen Y. Glycogen storage disease and other inherited disorders of carbohydrate metabolism. In: Kasper DL, Braunwald E, Fauci A, et al. eds. Harrison's Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2004.



Weinstein DA, Koeberl DD, Wolfsdorf JI. Type I Glycogen Storage Disease. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott, Williams and Wilkins; 2003:450-451.



JOURNAL ARTICLES

Dagli AI, Lee PJ, Correia CE, et al. Pregnancy in glycogen storage disease type Ib: gestational care and report of first successful deliveries. J Inherit Metab Dis. 2010.



Chou JY, Mansfield BC. Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease. Hum Mutat. 2008;29:921-30.



Franco LM, Krishnamurthy V, Bali D, et al. Hepatocellular carcinoma in glycogen storage disease type Ia: a case series. J Inherit Metab Dis. 2005;28:153-62.



Lewis R, Scrutton M, Lee P, Standen GR, Murphy DJ. Antenatal and Intrapartum care of a pregnant woman with glycogen storage disease type 1a. Eur J Obstet Gynecol Reprod Biol. 2005;118:111-2.



Ekstein J, Rubin BY, Anderson, et al. Mutation frequencies for glycogen storage disease in the Ashkenazi Jewish Population. Am J Med Genet A. 2004;129:162-4.



Melis D, Parenti G, Della Casa R, et al. Brain Damage in glycogen storage disease type I. J Pediatr. 2004;144:637-42.



Rake JP, Visser G, Labrune, et al. Guidelines for management of glycogen storage disease type I-European study on glycogen storage disease type I (ESGSD I). Eur J Pediatr. 2002b;161:112-9.



Rake JP Visser G, Labrune P, et al. Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European study on glycogen storage disease type I (EGGSD I). Eur J Pediat. 2002a;161:20-34.



Chou JY, Matern D, Mansfield, et al. Type I glycogen Storage diseases: disorders of the glucose-6-Phosphatase complex. Curr Mol Med. 2002;2:121-43.



Schwahn B, Rauch F, Wendel U, Schonau E. Low bone mass in glycogen storage disease type 1 is associated with reduced muscle force and poor metabolic control. J Pediatr. 2002;141:350-6.



Visser G, Rake JP, Labrune P, et al. Consensus guidelines for management of glycogen storage disease type 1b. Results of the European study on glycogen storage disease type I. Eur J Pediatr. 2002;161:120-3.



Weinstein DA and Wolfsdorf JI. Effect of continuous gucose therapy with uncooked cornstarch on the long-term clinical course of type 1a glycogen storage disease. Eur J Pediatr 2002;161:35-9.



Janecke AR, Mayatepek E, and Utermann G. Molecular genetics of type I glycogen storage disease. Mol Genet Metab. 2001;73:117-25.



Viser G, Rake JP, Fernandes, et al. Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type 1b: results of the European study on glycogen storage disease type I. J Pediatr. 2000;137:187-91.



Chen YT, Bazarre CH, Lee MM, et al. Type I glycogen storage disease: nine years of management with corn starch. Eur J Pediatr. 1993;152:56-9.



INTERNET

Bali DS, Chen YT, Goldstein JL. (Updated December 23, 2012). Glycogen Storage Disease Type I. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2011. Available at http://www.genetests.org. Accessed May 14, 2012.

Resources

CLIMB (Children Living with Inherited Metabolic Diseases)

Climb Building

176 Nantwich Road

Crewe, CW2 6BG

United Kingdom

Tel: 4408452412173

Fax: 4408452412174

Email: enquiries@climb.org.uk

Internet: http://www.CLIMB.org.uk



Association for Glycogen Storage Disease

P.O. Box 896

Durant, IA 52747

USA

Tel: (563)514-4022

Fax: (563)514-4022

Email: info@agsdus.org

Internet: http://www.agsdus.org



NIH/National Institute of Diabetes, Digestive & Kidney Diseases

Office of Communications & Public Liaison

Bldg 31, Rm 9A06

31 Center Drive, MSC 2560

Bethesda, MD 20892-2560

Tel: (301)496-3583

Email: NDDIC@info.niddk.nih.gov

Internet: http://www2.niddk.nih.gov/



Association for Glycogen Storage Disease (UK) Ltd

Old Hambledon Racecourse

Sheardley Lane, Droxford

Hampshire, SO32 3QY

United Kingdom

Tel: 03001232790

Email: info@agsd.org.uk

Internet: http://www.agsd.org.uk



Children's Fund for Glycogen Storage Disease Research, Inc.

917 Bethany Mountain Road

Cheshire, CT 06410

USA

Tel: (203)272-2873

Fax: (203)272-6695

Email: info@curegsd.org

Internet: http://www.cureGSD.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



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