Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Type III Glycogen Storage Disease Workup

  • Author: Wayne E Anderson, DO, FAHS, FAAN; Chief Editor: George T Griffing, MD  more...
 
Updated: Apr 25, 2014
 

Laboratory Studies

See the list below:

  • Because hypoglycemia may be found in some types of GSD, fasting glucose is indicated. Hypoglycemia is concerning and may lead to hypoglycemic seizures.
  • Urine studies are indicated because myoglobinuria may occur in some cases of GSD.
  • Hepatic failure occurs in some cases of GSD. Liver function studies are indicated.
  • The presence of dextrin is unique to Cori disease.
  • With a biochemical assay, debrancher enzyme activity is reduced or absent.
  • Hyperlipidemia is a common finding.
  • Fasting ketonemia is noted with the rapid metabolism of fatty acids.
Next

Imaging Studies

See the list below:

  • Imaging may reveal hepatomegaly.
  • Cardiomegaly may be present, but heart failure is not typical of GSD II.
Previous
Next

Other Tests

See the list below:

  • Ischemic forearm test
    • The ischemic forearm test is an important tool for diagnosis of muscle disorders. The basic premise is an analysis of the normal chemical reactions and products of muscle activity. Obtain consent before the test.
    • Instruct the patient to rest. Position a loosened blood pressure cuff on the arm and place a venous line for blood samples in the antecubital vein.
    • Obtain blood samples for the following tests: creatine kinase, ammonia, and lactate. Repeat in 5-10 minutes.
    • Obtain a urine sample for myoglobin analysis.
    • Immediately inflate the blood pressure cuff above systolic blood pressure and have the patient repetitively grasp an object, such as a dynamometer. Instruct the patient to grasp the object firmly, once or twice per second. Encourage the patient for 2-3 minutes, at which time the patient may no longer be able to participate. Immediately release and remove the blood pressure cuff.
    • Obtain blood samples for creatine kinase, ammonia, and lactate immediately and at 5, 10, and 20 minutes.
    • Collect a final urine sample for myoglobin analysis.
  • Interpretation of ischemic forearm test results
    • With exercise, carbohydrate metabolic pathways yield lactate from pyruvate. Lack of lactate production during exercise is evidence of pathway disturbance, and an enzyme deficiency is suggested. In such cases, muscle biopsy with biochemical assay is indicated.
    • Healthy patients demonstrate an increase in lactate of at least 5-10 mg/dL and ammonia of at least 100 µg/dL. Levels will return to baseline.
    • If neither level increases, the exercise was not strenuous enough and the test is not valid.
    • Increased lactate at rest (before exercise) is evidence of mitochondrial myopathy.
    • Failure of lactate to increase with ammonia is evidence of a GSD resulting in a block in carbohydrate metabolic pathways. Not all GSDs have a positive result on ischemic test.
    • Failure of ammonia to increase with lactate is evidence of myoadenylate deaminase deficiency.
    • In Cori disease, the ischemic forearm test result is positive.
  • Electromyography
    • Electromyography patterns are diverse and vary from patient to patient.
    • The myopathic finding of polyphasic responses is found, but amplitude and duration may be either decreased, as expected, or increased in some cases.
    • Spontaneous abnormal activity (fibrillation potential and positive sharp waves) may be found.
    • Myotonic discharges are observed in some cases.
Previous
Next

Histologic Findings

Muscle biopsy is periodic acid-Schiff positive with basophilic deposits in all tissues, including the CNS.

Previous
 
 
Contributor Information and Disclosures
Author

Wayne E Anderson, DO, FAHS, FAAN Assistant Professor of Internal Medicine/Neurology, College of Osteopathic Medicine of the Pacific Western University of Health Sciences; Clinical Faculty in Family Medicine, Touro University College of Osteopathic Medicine; Clinical Instructor, Departments of Neurology and Pain Management, California Pacific Medical Center

Wayne E Anderson, DO, FAHS, FAAN is a member of the following medical societies: California Medical Association, American Headache Society, San Francisco Medical Society, San Francisco Medical Society, International Headache Society, California Neurology Society, San Francisco Neurological Society, American Academy of Neurology, California Medical Association

Disclosure: Received honoraria from Teva for speaking and teaching; Received grant/research funds from Allergan for other; Received honoraria from Insys for speaking and teaching; Received honoraria from DepoMed for speaking and teaching.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Kent Wehmeier, MD Professor, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, St Louis University School of Medicine

Kent Wehmeier, MD is a member of the following medical societies: American Society of Hypertension, Endocrine Society, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

References
  1. Okubo M, Kanda F, Horinishi A, et al. Glycogen storage disease type IIIa: first report of a causative missense mutation (G1448R) of the glycogen debranching enzyme gene found in a homozygous patient. Hum Mutat. 1999 Dec. 14(6):542-3. [Medline].

  2. Aoyama Y, Ozer I, Demirkol M, et al. Molecular features of 23 patients with glycogen storage disease type III in Turkey: a novel mutation p.R1147G associated with isolated glucosidase deficiency, along with 9 AGL mutations. J Hum Genet. 2009 Nov. 54(11):681-6. [Medline].

  3. Cheng A, Zhang M, Okubo M, et al. Distinct mutations in the glycogen debranching enzyme found in glycogen storage disease type III lead to impairment in diverse cellular functions. Hum Mol Genet. 2009 Jun 1. 18(11):2045-52. [Medline]. [Full Text].

  4. Endo Y, Fateen E, El Shabrawy M, et al. Egyptian glycogen storage disease type III - identification of six novel AGL mutations, including a large 1.5 kb deletion and a missense mutation p.L620P with subtype IIId. Clin Chem Lab Med. 2009. 47(10):1233-8. [Medline].

  5. Mili A, Ben Charfeddine I, Mamaï O, Abdelhak S, Adala L, Amara A, et al. Molecular and biochemical characterization of Tunisian patients with glycogen storage disease type III. J Hum Genet. 2012 Mar. 57(3):170-5. [Medline].

  6. Lam CW, Lee AT, Lam YY, et al. DNA-based subtyping of glycogen storage disease type III: mutation and haplotype analysis of the AGL gene in Chinese. Mol Genet Metab. 2004 Nov. 83(3):271-5. [Medline].

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

  8. Ingle SA, Moulick ND, Ranadive NU, Khedekar K. Hepatocellular failure in glycogen storage disorder type 3. J Assoc Physicians India. 2004 Feb. 52:158-60. [Medline].

  9. Demo E, Frush D, Gottfried M, Koepke J, Boney A, Bali D. Glycogen storage disease type III-hepatocellular carcinoma a long-term complication?. J Hepatol. 2007 Mar. 46(3):492-8. [Medline].

  10. Kalkan Ucar S, Coker M, et al. A monocentric pilot study of an antioxidative defense and hsCRP in pediatric patients with glycogen storage disease type IA and III. Nutr Metab Cardiovasc Dis. 2009 Jul. 19(6):383-90. [Medline].

  11. Zingone A, Hiraiwa H, Pan CJ, et al. Correction of glycogen storage disease type 1a in a mouse model by gene therapy. J Biol Chem. 2000 Jan 14. 275(2):828-32. [Medline].

  12. Bijvoet AG, Van Hirtum H, Vermey M, et al. Pathological features of glycogen storage disease type II highlighted in the knockout mouse model. J Pathol. 1999 Nov. 189(3):416-24. [Medline].

  13. Valayannopoulos V, Bajolle F, Arnoux JB, Dubois S, Sannier N, Baussan C, et al. Successful treatment of severe cardiomyopathy in glycogen storage disease type III With D,L-3-hydroxybutyrate, ketogenic and high-protein diet. Pediatr Res. 2011 Dec. 70(6):638-41. [Medline].

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

  15. Amato AA. Acid maltase deficiency and related myopathies. Neurol Clin. 2000 Feb. 18(1):151-65. [Medline].

  16. Aminoff MJ. Electromyography in Clinical Practice. New York, NY: Churchill Livingstone; 1998.

  17. Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. 2000 Jan. 105(1):e10. [Medline].

  18. Chen Y. The Metabolic and Molecular Bases of Inherited Disease. Scriver CR, Beaudet AL, Sly WS, et al. Glycogen Storage Diseases. New York, NY: McGraw-Hill; 2001. 1521-51.

  19. Coleman RA, Winter HS, Wolf B, et al. Glycogen storage disease type III (glycogen debranching enzyme deficiency): correlation of biochemical defects with myopathy and cardiomyopathy. Ann Intern Med. 116(11):896-900. [Medline].

  20. Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen storage diseases. J Am Diet Assoc. 1993 Dec. 93(12):1423-30. [Medline].

  21. Gregory BL, Shelton GD, Bali DS, Chen YT, Fyfe JC. Glycogen storage disease type IIIa in curly-coated retrievers. J Vet Intern Med. 2007 Jan-Feb. 21(1):40-6. [Medline].

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

  23. Levin S, Moses SW, Chayoth R, et al. Glycogen storage disease in Israel. A clinical, biochemical and genetic study. Isr J Med Sci. 1967 May-Jun. 3(3):397-410. [Medline].

  24. Orho M, Bosshard NU, Buist NR, et al. Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0. J Clin Invest. 102(3):507-15. [Medline].

  25. 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. 69(1):16-23. [Medline].

  26. Smit GP, Fernandes J, Leonard JV, et al. The long-term outcome of patients with glycogen storage diseases. J Inherit Metab Dis. 13(4):411-8. [Medline].

  27. Stevens AN, Iles RA, Morris PG, Griffiths JR. Detection of glycogen in a glycogen storage disease by 13C nuclear magnetic resonance. FEBS Lett. 150(2):489-93. [Medline].

  28. Vincentiis S, Valente KD, Valente M. Polymicrogyria in glycogenosis type III: an incidental finding?. Pediatr Neurol. 2004 Aug. 31(2):143-5. [Medline].

  29. Wolfsdorf JI, Holm IA, Weinstein DA. Glycogen storage diseases. Phenotypic, genetic, and biochemical characteristics, and therapy. Endocrinol Metab Clin North Am. 1999 Dec. 28(4):801-23. [Medline].

Previous
Next
 
Metabolic pathways of carbohydrates.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.