Genetics of Glycogen-Storage Disease Type V Workup

  • Author: Edward J Cupler, MD, FAAN; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Aug 19, 2011
 

Laboratory Studies

  • Elevated serum creatine (Cr) kinase levels at rest are noted in McArdle disease (glycogen-storage disease type V).
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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.
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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.[4]
    • 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.[5]
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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 McAEnzyme histochemistry of 19-year-old male with McArdle disease.
  • Electron microscopy: Extensive accumulation of normal-appearing glycogen under the sarcolemma and between the myofilaments.
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Contributor Information and Disclosures
Author

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, and World Muscle Society

Disclosure: Genzyme Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching

Coauthor(s)

Robert D Steiner, MD  Credit Unions for Kids Professor of Pediatric Research; Faculty, Pediatrics, Molecular and Medical Genetics, and Program in Molecular and Cellular Biosciences; Vice Chair for Research in Pediatrics, Doernbecher Children's Hospital, Oregon Health and Science University; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research

Disclosure: Amicus Honoraria Consulting; Actelion Honoraria Consulting; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Consulting; Genzyme Honoraria Consulting; Shire Honoraria Consulting

Melissa P Wasserstein, MD  Associate Professor, Departments of Genetics and Genomic Sciences and Pediatrics, Mount Sinai School of Medicine

Melissa P Wasserstein, MD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

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, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

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, American Society of Gene Therapy, American Society of Human Genetics, Child Neurology Society, and Society for Inherited Metabolic Disorders

Disclosure: Genzyme Corporation Salary Management position

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.

Hagop Youssoufian, MD, MSc  Vice President of Clinical Research, ImClone Systems Incorporated

Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

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