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Glycogen Storage Disease, Type VI: 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 21, 2007

Differential Diagnoses

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

Workup

Laboratory Studies

  • Obtain a creatine kinase level in all cases of suspected glycogen storage disease (GSD).
  • Because hypoglycemia may be found in some types of GSD, fasting glucose testing is indicated. In Hers disease, hypoglycemia is a primary concern.
  • Urine studies are indicated because myoglobinuria may occur in some patients with GSDs.
  • Hepatic failure occurs in some patients with GSDs, although rarely in those with Hers disease. Liver function studies are indicated and may reveal evidence of hepatic injury.
  • Biochemical assay of enzyme activity is necessary for definitive diagnosis.

Imaging Studies

Findings from imaging studies may reveal hepatomegaly.

Other Tests

  • Ischemic forearm test
    • In the case of Hers disease, which is not associated with significant muscle involvement, the forearm ischemic test is most useful to help rule out other GSDs, most specifically Cori disease, McArdle disease, and Tarui disease. Test findings are expected to be negative in patients with Hers disease.
    • 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 a 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 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 patients with GSDs have positive ischemic test results.
    • Failure of ammonia to increase with lactate is evidence of myoadenylate deaminase deficiency.
    • Positive ischemic forearm test results may occur in patients with Cori disease, McArdle disease, and Tarui disease.
    • In patients with Hers disease, ischemic test results are negative.

Procedures

Liver biopsy may be required to diagnose the cause of hepatomegaly.

More on Glycogen Storage Disease, Type VI

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

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Further Reading

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Keywords

Hers disease, glycogen storage disease type VI, GSD type VI, enzyme defect, hepatomegaly, hypoglycemia, liver phosphorylase deficiency, glycogen storage disease, GSD, Hers' disease, GSD type 0, glycogen synthase deficiency, GSD type Ia, glucose-6-phosphatase deficiency, G-6-P deficiency, von Gierke disease, GSD type II, acid maltase deficiency, Pompe disease, GSD type III, debranching enzyme deficiency, Forbes-Cori disease, GSD type IV, GSD type V, myophosphorylase deficiency, McArdle disease, transglucosidase deficiency, Andersen disease, amylopectinosis, GSD type VII, phosphofructokinase deficiency, Tauri 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

David M Klachko, MBBCh, Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Missouri
David M Klachko, MBBCh is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, Endocrine Society, Missouri State Medical Association, and Sigma Xi
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, MD, Head, Vascular Division, Baker Medical Research Institute; Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, Director of General Internal Medicine, St Louis University
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, and Endocrine Society
Disclosure: Nothing to disclose.

 
 
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