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Glycogen Storage Disease, Type III: 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
Glycogen Storage Disease, Type VI
Glucose-6-Phosphatase Deficiency
Glycogen Storage Disease, Type VII
Glucose-6-Phosphate Dehydrogenase Deficiency
Hepatic Carcinoma, Primary
Glycogen Storage Disease, Type Ia
Hepatic Cysts
Glycogen Storage Disease, Type Ib
Hepatic Failure
Glycogen Storage Disease, Type II
Hypoglycemia
Glycogen Storage Disease, Type IV
Glycogen Storage Disease, Type V

Workup

Laboratory Studies

  • 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.

Imaging Studies

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

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 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.

Histologic Findings

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

More on Glycogen Storage Disease, Type III

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

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  2. 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. Nov 2004;83(3):271-5. [Medline].

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

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

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Further Reading

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Keywords

Cori disease, GSD type III, Illingworth-Cori-Forbes disease, amylo-1,6-glucosidase debrancher deficiency, glycogenosis III, debranching enzyme deficiency, limit dextrinosis, 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, Forbes-Cori disease, GSD type IV, transglucosidase deficiency, Andersen disease, amylopectinosis, GSD type V, myophosphorylase deficiency, McArdle disease, GSD type VI, phosphorylase deficiency, Hers disease, GSD type VII, phosphofructokinase deficiency, Tarui 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, 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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