eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Glycogen-Storage Disease Type V: Treatment & Medication

Author: Edward J Cupler, MD, Associate Professor of Neurology, Department of Neurology, Director, Neuromuscular Diseases Center, MDA Clinic Director, Oregon Health and Science University; Co-director, ALS Center of Oregon
Coauthor(s): Robert D Steiner, MD, Professor, Departments of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Oregon Health & Science University; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital and Doernbecher Children's Hospital; Co-Director: Pediatric and Child Health Research, Oregon Clinical and Translational Research Institute (CTSA).; Melissa P Wasserstein, MD, Associate Professor, Departments of Genetics and Genomic Sciences and Pediatrics, Mount Sinai School of Medicine; Cydney L Fenton, MD, FAAP, Consulting Staff, Department of Pediatric Endocrinology, Children's Hospital Medical Center of Akron
Contributor Information and Disclosures

Updated: Oct 12, 2009

Treatment

Medical Care

  • Therapies in patients with McArdle disease (glycogen-storage disease type V) are used in an attempt to bypass the metabolic block by providing glucose or fructose yield inconsistent results. Similarly, injection of glucagons yields inconsistent results.

Consultations

  • Acute renal failure may occur with rhabdomyolysis, necessitating consultation with a nephrologist.
  • Monitor renal function in all patients with McArdle disease. This may be performed in conjunction with a nephrologist.

Diet

  • A high carbohydrate diet may improve maximal work capacity and exercise tolerance. A randomized controlled trial comparing a carbohydrate rich (20% fat, 15% protein, 65% carbohydrate) and a protein rich diet (15% fat, 55% protein, 30% carbohydrate) surprisingly showed that subjects on the carbohydrate rich diet improved exercise tolerance and maximum oxidative capacity compared with subjects on the protein rich diet.6

Activity

  • Regular, moderate aerobic activity has been shown to improve exercise capacity in patients with McArdle disease. Patients should exercise using a heart rate monitor, keeping the heart rate to 60-70% of maximum.7 Exercise should be preceded by a warm-up period and dose of sucrose prior to exertion if not contraindicated.8
  • Strenuous isometric exercises may cause symptoms or rhabdomyolysis.

Medication

In general, no specific treatment is indicated for McArdle disease (glycogen-storage disease type V). Vitamins such as vitamin B-6 (pyridoxine) may be beneficial to correct depleted body stores and augment myophosphorylase activity. Sucrose may improve exercise tolerance. Creatine may improve ATP capacity and exercise tolerability.

Other treatments, such as d-ribose, glucagon, verapamil, and dantrolene, have not been shown to be effective. Branched-chain amino acids were shown to worsen functional activity and exercise capacity.

Vitamins

These agents are necessary to promote regular growth and good health. Some studies suggest that pyridoxine may reduce the susceptibility of muscles to fatigue in patients with McArdle disease. Normally, myophosphorylase uses pyridoxal 5'-phosphate (derived from vitamin B-6) as a cofactor; therefore, supplementation may augment the remaining myophosphorylase activity. In addition, most of the total body pool of pyridoxine is normally bound to myophosphorylase; therefore, the body's store of pyridoxine may be depleted in patients with McArdle disease.


Pyridoxine (Nestrex)

Vitamin B-6 is a naturally occurring vitamin normally found in beans, grains, liver, meats, eggs, and vegetables.

Adult

100 mg/d PO

Pediatric

1-3 years: 30 mg/d PO
4-8 years: 40 mg/d PO
9-13 years: 60 mg/d PO
14-18 years: 80 mg/d PO

Pyridoxine may decrease serum levels of levodopa, phenytoin, and phenobarbital

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Adverse effects due to overdosage include headache, nausea, vomiting, seizures, tingling, pain, and numbness in the extremities

Nutritional Agent

Sucrose is a disaccharide that is readily split into glucose and fructose. These sugars circumvent the metabolic block in individuals with McArdle disease. Recently, sucrose (75 g 30 min PO before exercise) was shown to improve exercise tolerance to the point that no "second wind" phenomenon is observed.


Sucrose

Disaccharide from sugar cane made up of d-glucose and d-fructose.

Adult

75 g 30 min before exercise

Pediatric

Not established

Documented hypersensitivity; diabetes mellitus type I or type II

Pregnancy

A - Safe in pregnancy

Precautions

High doses may cause nausea and weight gain

Nutritional Supplement

Creatine monohydrate supplementation may increase ATP availability and exercise capacity. A single study demonstrated an increase in exercise capacity while low-dose creatine monohydrate (60 mg/kg/d) was administered. Interestingly, a subsequent study by the same group revealed a deleterious effect at a dosage of 150 mg/kg/d.9


Creatine monohydrate

Increases intracellular creatine and phosphocreatine levels. Converted to creatinine. Theorized to increase short-term energy supply to muscle tissue by rephosphorylation of ADP. Unknown if increased creatine in muscle improves athletic performance in nondepleted conditions.

Adult

60 mg/kg/d PO

Pediatric

Not established

Avoid coadministration with diuretics because of increased risk of dehydration and related toxicity; caution with drugs that impair renal function (eg, NSAIDs, probenecid, aminoglycosides, cyclosporine, antineoplastic agents)

Documented hypersensitivity; renal impairment; diuretic use or dehydration

Pregnancy

C - Safety for use during pregnancy has not been established

Precautions

Monitor serum creatinine levels; may cause muscle cramps, particularly if dehydrated; may contain contaminants because no official standards are established for manufacturing regulation; no human or animal teratogenicity data are available; avoid during pregnancy or lactation

Angiotensin-Converting Enzyme (ACE) Inhibitor

Investigators studying a small cohort of 8 adult patients reported that treatment with 2.5 mg of ramipril subjectively improved reported scores of perceived disability but had no effect on objective functional outcomes measures. The improvement in the perceived disability scores was more pronounced in the D/D genotype and was absent in the I/D genotype. Although not significant, the D/D genotype also showed a slight improvement in peak VO2. The improvement in peak VO2 and subjective disability scores suggest a benefit of ramipril treatment in patients with the D/D genotype, but additional testing of a larger patient population is needed.10


Ramipril (Altace)

Prevents conversion of Angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Adult

2.5-5 mg PO qd; not to exceed 20 mg/d

Pediatric

Not established

NSAIDs may reduce hypotensive effects of ramipril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases ramipril levels; probenecid may increase ramipril levels; the hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics

Documented hypersensitivity; history of angioedema

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal impairment, valvular stenosis, or severe congestive heart failure

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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Further Reading

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Keywords

glycogen-storage disease type V, GSD type V, GSD V, McArdle syndrome, McArdle's syndrome, myophosphorylase deficiency, phosphorylase deficiency, McArdle disease, McArdle's disease, McArdle myopathy, McArdle's myopathy, muscle glycogen phosphorylase deficiency, glycogen storage disease type V, acute muscle necrosis, myoglobinuria, glycogen-storage disease type V, glycogen storage disease type VI, glycogen-storage disease type VI, Hers disease, exercise intolerance, early fatigue, treatment, diagnosis

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Contributor Information and Disclosures

Author

Edward J Cupler, MD, Associate Professor of Neurology, Department of Neurology, Director, Neuromuscular Diseases Center, MDA Clinic Director, Oregon Health and Science University; Co-director, ALS Center of Oregon
Edward J Cupler, MD 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

Coauthor(s)

Robert D Steiner, MD, Professor, Departments of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Oregon Health & Science University; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital and Doernbecher Children's Hospital; Co-Director: Pediatric and Child Health Research, Oregon Clinical and Translational Research Institute (CTSA).
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: Genzyme Honoraria Speaking and teaching; Genzyme Grant/research funds Other; Shire Honoraria Speaking and teaching; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Speaking and teaching; Biomarin Consulting fee Consulting; Amicus  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, FAAP, Consulting Staff, Department of Pediatric Endocrinology, Children's Hospital Medical Center of Akron
Cydney L Fenton, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

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

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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.

CME Editor

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, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, 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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