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

Workup

Laboratory Studies

  • Obtain a creatine kinase level in all cases of suspected GSD. Creatine kinase levels are elevated in more than 90% of patients with McArdle disease. Bruno and colleagues report a case of elevated creatine kinase on routine screening as the only sign of McArdle disease in a 13-year-old boy.6
  • Because hypoglycemia may be found in some types of GSD, fasting glucose testing is indicated. Hypoglycemia is of concern and may lead to hypoglycemic seizures.
  • Urine studies are indicated because myoglobinuria may occur in some patients with GSDs.
  • Hepatic failure occurs in some patients with GSDs. Liver function studies are indicated. In general, the liver contains little myophosphorylase.
  • Myoglobinuria is found in 50% of patients after exercise.
  • Biochemical assay is required for definitive diagnosis. Phosphorylase reaction is absent.

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 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 a positive ischemic test result.
    • Failure of ammonia to increase with lactate is evidence of myoadenylate deaminase deficiency.
    • If a patient has McArdle disease, the ischemic forearm test results are positive.
  • Electromyography
    • In contrast to most GSDs, findings upon electromyography may be normal.
    • Findings from electromyography of resting muscle are normal.
    • Electrical activity is absent during contracture.
    • Repetitive nerve stimulation at low frequency (2 Hz) does not demonstrate an abnormal response, although repetitive stimulation at high frequency (15 Hz) may produce a decrement with contracture formation.
    • Single-fiber electromyography may reveal increased jitter.

Procedures

Muscle biopsy is necessary for assay of muscle enzyme activity.

Histologic Findings

Muscle biopsy findings may reveal fiber size variability, positive subsarcolemmal blebs with periodic acid-Schiff stain, and intermyofibril vacuoles. Felice and colleagues (1996) report selective atrophy of type 1 muscle fibers.7

More on Glycogen Storage Disease, Type V

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

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  2. Felice KJ, Schneebaum AB, Jones HR Jr. McArdle's disease with late-onset symptoms: case report and review of the literature. J Neurol Neurosurg Psychiatry. May 1992;55(5):407-8. [Medline].

  3. Pourmand R, Sanders DB, Corwin HM. Late-onset Mcardle''s disease with unusual electromyographic findings. Arch Neurol. Jun 1983;40(6):374-7. [Medline].

  4. Braakhekke JP, de Bruin MI, Stegeman DF. The second wind phenomenon in McArdle's disease. Brain. 109 (Pt 6):1087-101. [Medline].

  5. Voduc N, Webb KA, D'Arsigny C, et al. McArdle's disease presenting as unexplained dyspnea in a young woman. Can Respir J. Mar 2004;11(2):163-7. [Medline].

  6. Bruno C, Bertini E, Santorelli FM. HyperCKemia as the only sign of McArdle''s disease in a child. J Child Neurol. Feb 2000;15(2):137-8. [Medline].

  7. Felice KJ, Grunnet ML, Sima AA. Selective atrophy of type 1 muscle fibers in McArdle's disease. Neurology. Aug 1996;47(2):581-3. [Medline].

  8. 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].

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  15. Chen Y. Glycogen Storage Diseases. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B, eds. The Metabolic and Molecular Bases of Inherited Disease. Vol 1. 8th ed. New York, NY: McGraw-Hill; 2000:1537-8.

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  19. Isackson PJ, Tarnopolsky M, Vladutiu GD. A novel mutation in the PYGM gene in a family with pseudo-dominant transmission of McArdle disease. Mol Genet Metab. Jul 2005;85(3):239-42. [Medline].

  20. Martin MA, Rubio JC, Campos Y. Two homozygous mutations (R193W and 794/795 delAA) in the myophosphorylase gene in a patient with McArdle's disease. Hum Mutat (Online). Mar 2000;15(3):294. [Medline].

  21. O'Dochartaigh CS, Ong HY, Lovell SM, et al. Oxygen consumption is increased relative to work rate in patients with McArdle's disease. Eur J Clin Invest. Nov 2004;34(11):731-7. [Medline].

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  23. Pillarisetti J, Ahmed A. McArdle disease presenting as acute renal failure. South Med J. Mar 2007;100(3):313-6. [Medline].

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Further Reading

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Keywords

McArdle disease, McArdle’s disease, glycogen storage disease type V, GSD type V, myophosphorylase deficiency, enzyme defect, glycogen storage disease, GSD, 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, transglucosidase deficiency, Andersen disease, amylopectinosis, 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

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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