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Genetics of Glycogen-Storage Disease Type V Workup

  • Author: Edward J Cupler, MD, FAAN; Chief Editor: Maria Descartes, MD  more...
Updated: Nov 10, 2015

Laboratory Studies

Elevated serum creatine (Cr) kinase levels at rest are noted in McArdle disease (glycogen-storage disease type V).


Imaging Studies

Phosphorous 31-nuclear magnetic resonance (31P-NMR) findings reveal a lack of cytoplasmic acidification during exercise and a greater-than-normal drop in recalculating Cr/inorganic phosphate (Pi) ratio.


Other Tests

Electromyography (EMG)

One half of patients may have nonspecific myopathic changes. Some patients have signs of increased muscle irritability. During exercise-induced cramps, electrical activity may be absent on EMG.

Ischemic forearm exercise test

Patient squeezes a handgrip dynamometer at maximal voluntary contraction (MVC) while a blood pressure cuff is inflated to 250 mm Hg on the upper arm. The exercise lasts for 1 minute, with 1 second contractions followed by 1 second rests. A positive test result occurs if no increase in venous lactic acid levels or pyruvate levels is observed following the exercise.

Compartment syndrome has induced by the ischemic forearm test. The test may also provide false positives in patients who are severely weak or less motivated or in the presence of other glycolytic defects.[9]

Nonischemic forearm testing provides the same level of diagnostic ability with less risk of compartment syndrome. This is performed in the same manner but without the use of the blood pressure cuff.[10]


Histologic Findings

Muscle biopsy

Subsarcolemmal deposits of glycogen appear at the periphery of myofibers. Accumulation of glycogen between myofibrils may give the fibers a vacuolar appearance. The glycogen is periodic acid-Schiff (PAS) positive. Glycogen may be washed out when the tissue is processed. Therefore, the lack of apparent glycogen accumulation on muscle biopsy findings does not rule out the condition.

Enzyme histochemistry for myophosphorylase is easy to perform and when absent is diagnostic for McArdle disease. However, because this is not routinely performed, clinicians must specifically request myophosphorylase testing. Quantitative analysis of myophosphorylase in muscle tissue is also available at specialty laboratories. See the image below.

Enzyme histochemistry of 19-year-old male with McA Enzyme histochemistry of 19-year-old male with McArdle disease.

Electron microscopy

Extensive accumulation of normal-appearing glycogen under the sarcolemma and between the myofilaments.

Contributor Information and Disclosures

Edward J Cupler, MD, FAAN Head of Neurophysiology Section, Director of Neurology Residency Training Program, Consultant in Neurology, Neuromuscular Disorders, and Sports Neurology, King Faisal Specialist Hospital and Research Center, Saudi Arabia

Edward J Cupler, MD, FAAN is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, World Muscle Society

Disclosure: Received honoraria from Genzyme for speaking and teaching; Received honoraria from Pfizer for speaking and teaching.


Cydney L Fenton, MD Director, Center for Diabetes and Endocrinology, Akron Children's Hospital

Cydney L Fenton, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, Endocrine Society, Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Edward Kaye, MD Vice President of Clinical Research, Genzyme Corporation

Edward Kaye, MD is a member of the following medical societies: American Academy of Neurology, Society for Inherited Metabolic Disorders, American Society of Gene and Cell Therapy, American Society of Human Genetics, Child Neurology Society

Disclosure: Received salary from Genzyme Corporation for management position.

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Enzyme histochemistry of 19-year-old male with McArdle disease.
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