Genetics of Glycogen-Storage Disease Type III Medication

  • Author: David H Tegay, DO, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 13, 2012
 

Medication Summary

Glucose—oral, enteral, and intravenous forms—is used to manage hypoglycemic episodes. Glucagon administration may have value for managing hypoglycemic episodes. For patients with a concurrent illness, pay particular attention to ensuring an adequate intake of glucose and glucose precursors.

Next

Monosaccharides

Class Summary

Dextrose is a metabolic substrate and simple sugar.

View full drug information

Dextrose (D-Glucose)

 

Absorbed rapidly from the small intestine and then distributed to other tissues. Administer parenterally injected dextrose to patients who cannot maintain adequate PO intake or to patients with hypoglycemia who require rapidly increased blood glucose levels. Concentrated dextrose infusions provide large amounts of glucose in a small volume. Paradoxically, rebound hypoglycemia can be produced if hyperinsulinemia is induced by excessively raising serum glucose levels.

Previous
Next

Glucogen-stimulating agent

Class Summary

Pancreatic alpha cells of the islets of Langerhans produce glucagon, a polypeptide hormone, which exerts opposite effects of insulin on blood glucose. Glucagon elevates blood glucose levels by inhibiting glycogen synthesis and by enhancing glucose formation from noncarbohydrate sources such as proteins and fats (ie, gluconeogenesis). The most important role of glucagon in treating GSD III is to stimulate glycogenolysis in the liver.

View full drug information

Glucagon

 

Polypeptide (single chain) with 29 amino acid residues and a molecular weight of 3483. Acts only on liver glycogen to release glucose via a complex series of reactions involving cAMP, epinephrine, phosphorylase, and phosphorylase kinase. May be useful when IV access is problematic and dextrose cannot be administered.

Previous
Proceed to Follow-up
 
 
Contributor Information and Disclosures
Author

David H Tegay, DO, FACMG  Associate Professor of Medicine and Medical Genetics, New York College of Osteopathic Medicine at the New York Institute of Technology; Assistant Professor of Pediatrics, Stony Brook University Medical Center

David H Tegay, DO, FACMG is a member of the following medical societies: American College of Medical Genetics, American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Osteopathic Association, American Society of Human Genetics, and Federation of American Societies for Experimental Biology

Disclosure: Nothing to disclose.

Coauthor(s)

Riya Jose  Medicine Department Academic Fellow, New York College of Osteopathic Medicine of the New York Institute of Technology

Disclosure: Nothing to disclose.

Specialty Editor Board

Edward Kaye, MD  Vice President of Clinical Research, Genzyme Corporation

Edward Kaye, MD is a member of the following medical societies: American Academy of Neurology, American Society of Gene Therapy, American Society of Human Genetics, Child Neurology Society, and Society for Inherited Metabolic Disorders

Disclosure: Genzyme Corporation Salary Management position

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Hagop Youssoufian, MD, MSc  Vice President of Clinical Research, ImClone Systems Incorporated

Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Howard R Sloan, MD, PhD to the development and writing of this article.

References

  1. Chen YT. A novel point mutation in an acceptor splice site of intron 32 (IVS32 A-12®G) but no exon 3 mutations in the glycogen debranching enzyme gene in a homozygous patient with glycogen storage disease type IIIb. Hum Genet. Jan 1999;104(1):111-2. [Medline].

  2. Chen YT. The Metabolic and Molecular Bases of Inherited Disease. Vol 1. New York, NY: McGraw Hill; 2001:1521-51.

  3. Forbes G. Glycogen Storage Disease. Report of a case with abnormal glycogen structure in liver and skeletal muscle. J Pediatr. 1953;42:645-52.

  4. Illingworth B, Cori G. Structure of glycogens and amylopectins, III. Normal and abnormal human glycogen. J Biol Chem. 1952;199:653-9.

  5. Illingworth B, Cori G, Cori C. Amylo-1,6-glucosidase in muscle tissue in generalized glycogen storage disease. J Biol Chem. 1956;218:123-30.

  6. Snappes I, Van Creveld S. Un cas d'hypoglycemie avec acetonemie chez un enfant. Bull Mem Soc Med Hop (Paris). 1928;52:1315-7.

  7. Demo E, Frush D, Gottfried M, et al. Glycogen storage disease type III-hepatocellular carcinoma a long-term complication?. J Hepatol. Mar 2007;46(3):492-8. [Medline].

  8. Coleman RA, Winter HS, Wolf B, Chen YT. Glycogen debranching enzyme deficiency: long-term study of serum enzyme activities and clinical features. J Inherit Metab Dis. 1992;15(6):869-81. [Medline].

  9. Labrune P, Trioche P, Duvaltier I, et al. Hepatocellular adenomas in glycogen storage disease type I and III: a series of 43 patients and review of the literature. J Pediatr Gastroenterol Nutr. Mar 1997;24(3):276-9. [Medline].

  10. Shen J, Bao Y, Liu HM, et al. Mutations in exon 3 of the glycogen debranching enzyme gene are associated with glycogen storage disease type III that is differentially expressed in liver and muscle. J Clin Invest. Jul 15 1996;98(2):352-7. [Medline].

  11. Shin YS. Glycogen storage disease: clinical, biochemical, and molecular heterogeneity. Semin Pediatr Neurol. Jun 2006;13(2):115-20. [Medline].

  12. Zimakas PJ, Rodd CJ. Glycogen storage disease type III in Inuit children. CMAJ. Feb 1 2005;172(3):355-8. [Medline]. [Full Text].

  13. Santer R, Kinner M, Steuerwald U, et al. Molecular genetic basis and prevalence of glycogen storage disease type IIIA in the Faroe Islands. Eur J Hum Genet. May 2001;9(5):388-91. [Medline].

  14. Parvari R, Moses S, Shen J, Hershkovitz E, Lerner A, Chen YT. A single-base deletion in the 3'-coding region of glycogen-debranching enzyme is prevalent in glycogen storage disease type IIIA in a population of North African Jewish patients. Eur J Hum Genet. Sep-Oct 1997;5(5):266-70. [Medline].

  15. Lee PJ, Deanfield JE, Burch M, et al. Comparison of the functional significance of left ventricular hypertrophy in hypertrophic cardiomyopathy and glycogenosis type III. Am J Cardiol. Mar 15 1997;79(6):834-8. [Medline].

  16. Cleary MA, Walter JH, Kerr BA, Wraith JE. Facial appearance in glycogen storage disease type III. Clin Dysmorphol. Apr 2002;11(2):117-20. [Medline].

  17. Hadjigeorgiou GM, Comi GP, Bordoni A, et al. Novel donor splice site mutations of AGL gene in glycogen storage disease type IIIa. J Inherit Metab Dis. Aug 1999;22(6):762-3. [Medline].

  18. DiMauro S, Hartwig GB, Hays A, et al. Debrancher deficiency: neuromuscular disorder in 5 adults. Ann Neurol. May 1979;5(5):422-36. [Medline].

  19. Bernier AV, Sentner CP, Correia CE, et al. Hyperlipidemia in glycogen storage disease type III: effect of age and metabolic control. J Inherit Metab Dis. Dec 2008;31(6):729-32. [Medline].

  20. Manwaring V, Prunty H, Bainbridge K, Burke D, Finnegan N, Franses R, et al. Urine analysis of glucose tetrasaccharide by HPLC; a useful marker for the investigation of patients with Pompe and other glycogen storage diseases. J Inherit Metab Dis. Mar 2012;35(2):311-6. [Medline].

  21. Lucchiari S, Pagliarani S, Salani S, et al. Hepatic and neuromuscular forms of glycogenosis type III: nine mutations in AGL. Hum Mutat. Jun 2006;27(6):600-1. [Medline].

  22. Schüller A, Wenninger S, Strigl-Pill N, Schoser B. Toward deconstructing the phenotype of late-onset Pompe disease. Am J Med Genet C Semin Med Genet. Feb 15 2012;160(1):80-8. [Medline].

  23. Lee P, Mather S, Owens C, et al. Hepatic ultrasound findings in the glycogen storage diseases. Br J Radiol. Nov 1994;67(803):1062-6. [Medline].

  24. Markowitz AJ, Chen YT, Muenzer J, et al. A man with type III glycogenosis associated with cirrhosis and portal hypertension. Gastroenterology. Dec 1993;105(6):1882-5. [Medline].

  25. Gremse DA, Bucuvalas JC, Balistreri WF. Efficacy of cornstarch therapy in type III glycogen-storage disease. Am J Clin Nutr. Oct 1990;52(4):671-4. [Medline].

  26. Haagsma EB, Smit GP, Niezen-Koning KE, et al. Type IIIb glycogen storage disease associated with end-stage cirrhosis and hepatocellular carcinoma. The Liver Transplant Group. Hepatology. Mar 1997;25(3):537-40. [Medline].

  27. Iyer SG, Chen CL, Wang CC, et al. Long-term results of living donor liver transplantation for glycogen storage disorders in children. Liver Transpl. Jun 2007;13(6):848-52. [Medline].

  28. Matern D, Starzl TE, Arnaout W, et al. Liver transplantation for glycogen storage disease types I, III, and IV. Eur J Pediatr. Dec 1999;158 Suppl 2:S43-8. [Medline].

  29. Shen J, Liu HM, McConkie-Rosell A, Chen YT. Prenatal diagnosis and carrier detection for glycogen storage disease type III using polymorphic DNA markers. Prenat Diagn. Jan 1998;18(1):61-4. [Medline].

  30. Yang BZ, Ding JH, Brown BI, Chen YT. Definitive prenatal diagnosis for type III glycogen storage disease. Am J Hum Genet. Oct 1990;47(4):735-9. [Medline].

  31. Bhuiyan J, Al Odaib AN, Ozand PT. A simple, rapid test for the differential diagnosis of glycogen storage disease type 3. Clin Chim Acta. Sep 2003;335(1-2):21-6. [Medline].

  32. Okuda S, Kanda F, Takahashi K, et al. Fatal liver cirrhosis and esophageal variceal hemorrhage in a patient with type IIIa glycogen storage disease. Intern Med. Dec 1998;37(12):1055-7. [Medline].

  33. Shaiu WL, Kishnani PS, Shen J, et al. Genotype-phenotype correlation in two frequent mutations and mutation update in type III glycogen storage disease. Mol Genet Metab. Jan 2000;69(1):16-23. [Medline].

  34. Shen JJ, Chen YT. Molecular characterization of glycogen storage disease type III. Curr Mol Med. Mar 2002;2(2):167-75. [Medline].

  35. Siciliano M, De Candia E, Ballarin S, et al. Hepatocellular carcinoma complicating liver cirrhosis in type IIIa glycogen storage disease. J Clin Gastroenterol. Jul 2000;31(1):80-2. [Medline].

  36. Van Creveld S. Chronische hepatogene Hypoglykamie im Kindesalter. Z Kindern. 1932;52:299.

  37. Van Creveld S, Huijing F. Differential diagnosis of the type of glycogen disease in two adult patients with long history of glycogenosis. Metabolism. 1964;13:191-8.

  38. Wolfsdorf JI, Crigler JF Jr. Effect of continuous glucose therapy begun in infancy on the long-term clinical course of patients with type I glycogen storage disease. J Pediatr Gastroenterol Nutr. Aug 1999;29(2):136-43. [Medline].

 
Previous
Next
 
Schematic illustration of the degradation of glycogen by the concerted action of the enzymes phosphorylase and debranching enzyme. First, phosphorylase removes glucose moieties (linked to their neighbors via alpha1,4 glucosidic bonds and depicted as the 7 black circles) from the unbranched outer portions of the glycogen molecule until only 4 glucosyl units (depicted as the 3 green circles and the 1 red circle) remain before an alpha1,6 branch point. The transferase component of debranching enzyme then transfers the 3 (green) glucose residues from the short branch to the end of an adjacent branch of the glycogen molecule. The glucosidase component of debranching enzyme then removes the glucose moiety (depicted as the red circle) remaining at the alpha1,6 branch point. In the process, the branch point formed by the alpha1,6 glucosidic bond is removed, hence the name debrancher.Unlike phosphorylase, which removes glucose moieties from glycogen in the form of glucose-1-phosphate, debrancher releases 1 free glucose moiety from each branch point. After the cleavage of the branch site, phosphorylase attacks unbranched portions of the glycogen molecule until the enzyme is stymied by the appearance of another branch point, at which point debranching enzyme once again is called into play. Eventually, large portions of the glycogen molecule are degraded to free glucose by the action of the amylo-alpha1,6-glucosidase activity of debranching enzyme and to glucose-1-phosphate by the action of phosphorylase.
Schematic representation of a portion of a molecule of glycogen. Open circles represent the glucose moieties connected to each other via alpha1,4 linkages. Solid circles represent the glucose moieties connected to their neighbors via alpha1,6 linkages. Thus, each solid circle represents a branch point in the molecule.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.