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Glycogen Storage Disease, Type II: Differential Diagnoses & Workup

Author: Wayne E Anderson, DO, Assistant Professor of Internal Medicine/Neurology, Western University of Health Sciences; Assistant Professor of Family Medicine, Touro University College of Osteopathic Medicine; Consulting Staff in Pain Management, Department of Neurology, California Pacific Medical Center
Contributor Information and Disclosures

Updated: Sep 20, 2007

Differential Diagnoses

Glucose Intolerance
Hepatic Carcinoma, Primary
Glucose-6-Phosphatase Deficiency
Hepatic Cysts
Glucose-6-Phosphate Dehydrogenase Deficiency
Hepatic Failure
Glycogen Storage Disease, Type Ib
Hypoglycemia
Glycogen Storage Disease, Type V
Glycogen Storage Disease, Type VI

Workup

Laboratory Studies

  • Obtain a creatine kinase in all cases of suspected GSD. Creatine kinase is elevated in Pompe disease.
  • Because hypoglycemia may be found in some types of GSD, fasting glucose is indicated. Because the liver phosphorylase is not involved (only muscle phosphorylase), hypoglycemia is not an expected finding.
  • Urine studies are indicated because myoglobinuria may occur in some GSDs.
  • Hepatic failure occurs in some GSDs. Liver function studies are indicated.
  • Biochemical assay is required for definitive diagnosis. Assay reveals deficient acid maltase in fibroblasts.

Imaging Studies

  • Aneurysms, which represent glycogen storage within the intracranial vasculature, may be found on angiography or magnetic resonance angiography.
  • Consider echocardiography to assess heart size and amount of left ventricular hypertrophy.

Other Tests

  • 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 mcg/dL. Levels return to baseline.
    • If neither level increases, the exercise was not strenuous enough and the test result 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 ischemic test result.
    • Failure of ammonia to increase with lactate is evidence of myoadenylate deaminase deficiency.
    • Findings on the ischemic forearm test are normal in Pompe disease.
  • Electromyelography
    • In 1998, Aminoff reported electromyelographic findings suggestive of a myopathy, although abnormal spontaneous activity may be present.4
    • Electrical myotonia without clinical myotonia may be present.
    • Myotonic discharges may be found in the paraspinal muscles.
    • Fibrillation potentials, positive sharp waves, and complex repetitive discharges may be found.
    • Myopathic findings of polyphasic responses, decreased duration of potentials, and decreased amplitude are usually present.
  • Electrocardiography: ECG demonstrates a pan-lead short PR interval and elevated QRS complexes in the infantile form. A case of Wolff-Parkinson-White syndrome has been reported in association with Pompe disease.

Procedures

  • Muscle biopsy assists with the evaluation of muscle weakness.

Histologic Findings

Muscle biopsy shows vacuolar myopathy. Type I fibers are most often involved. Lysosomal glycogen accumulates are predominant, although the cytoplasm may be involved. Periodic acid-Schiff stain is positive for inclusions.

More on Glycogen Storage Disease, Type II

Overview: Glycogen Storage Disease, Type II
Differential Diagnoses & Workup: Glycogen Storage Disease, Type II
Treatment & Medication: Glycogen Storage Disease, Type II
Follow-up: Glycogen Storage Disease, Type II
Multimedia: Glycogen Storage Disease, Type II
References
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References

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

  2. Gort L, Coll MJ, Chabás A. Glycogen storage disease type II in Spanish patients: High frequency of c.1076-1G>C mutation. Mol Genet Metab. Sep-Oct 2007;92(1-2):183-7. [Medline].

  3. Martiniuk F, Chen A, Mack A. Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease. Am J Med Genet. Aug 27 1998;79(1):69-72. [Medline].

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

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

  6. Bijvoet AG, Van Hirtum H, Kroos MA. Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II. Hum Mol Genet. Nov 1999;8(12):2145-53. [Medline].

  7. Phupong V, Shotelersuk V. Prenatal exclusion of Pompe disease by electron microscopy. Southeast Asian J Trop Med Public Health. Sep 2006;37(5):1021-4. [Medline].

  8. Mah C, Cresawn KO, Fraites TJ Jr, Pacak CA, Lewis MA, Zolotukhin I. Sustained correction of glycogen storage disease type II using adeno-associated virus serotype 1 vectors. Gene Ther. Sep 2005;12(18):1405-9. [Medline].

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

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

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

  12. Hirshhorn R, Reuser A. Glycogen Storage Disease Type II: Acid alpha-Glucosidase (Acid Maltase) Deficiency. In: The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2001:3389-3420.

  13. Melvin JJ. Pompe's disease. Arch Neurol. Jan 2000;57(1):134-5. [Medline].

  14. Orho M, Bosshard NU, Buist NR. Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0. J Clin Invest. Aug 1 1998;102(3):507-15. [Medline].

  15. Sahin M, du Plessis AJ. Hydrocephalus associated with glycogen storage disease type II (Pompe's disease). Pediatr Neurol. Sep 1999;21(3):674-6. [Medline].

  16. Smit GP, Fernandes J, Leonard JV. The long-term outcome of patients with glycogen storage diseases. J Inherit Metab Dis. 1990;13(4):411-8. [Medline].

  17. Stevens AN, Iles RA, Morris PG. Detection of glycogen in a glycogen storage disease by 13C nuclear magnetic resonance. FEBS Lett. Dec 27 1982;150(2):489-93. [Medline].

  18. Sun B, Zhang H, Franco LM, Brown T, Bird A, Schneider A. Correction of glycogen storage disease type II by an adeno-associated virus vector containing a muscle-specific promoter. Mol Ther. Jun 2005;11(6):889-98. [Medline].

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

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Further Reading

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Keywords

Pompe disease, acid maltase deficiency, type II glycogen storage disease, glycogen storage disease, GSD type II, lysosomal alpha-1,4-glucosidase deficiency, Cori disease, GSD type III, debranching enzyme deficiency, McArdle disease, GSD type V, myophosphorylase deficiency, Tarui disease, GSD type VII, phosphofructokinase deficiency, von Gierke disease, GSD type Ia, glucose-6-phosphatase deficiency, enzyme defects, glycogen accumulation, glycogen synthase deficiency, glucose-6-phosphatase deficiency, G-6-P deficiency, Pompe disease, Forbes-Cori disease, GSD type IV, transglucosidase deficiency, Andersen disease, amylopectinosis, GSD type VI, phosphorylase deficiency, Hers disease

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Contributor Information and Disclosures

Author

Wayne E Anderson, DO, Assistant Professor of Internal Medicine/Neurology, Western University of Health Sciences; Assistant Professor of Family Medicine, Touro University College of Osteopathic Medicine; Consulting Staff in Pain Management, Department of Neurology, California Pacific Medical Center
Wayne E Anderson, DO is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American Medical Association, American Society of Law Medicine and Ethics, California Medical Association, and San Francisco Medical Society
Disclosure: Cephalon Honoraria Speaking and teaching; Janssen Honoraria Speaking and teaching; Ligand Honoraria Consulting; Alpharma Honoraria Speaking and teaching

Medical Editor

Barry J Goldstein, MD, PhD, Director, Division of Endocrinology, Diabetes and Metabolic Diseases, Professor, Department of Internal Medicine, Thomas Jefferson University
Barry J Goldstein, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, and Endocrine Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor 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, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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