eMedicine Specialties > Endocrinology > Metabolic Disorders

Glycogen Storage Disease, Type II (Pompe Disease): Treatment & Medication

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; Consulting Staff in Neurology, Department of Neurology, California Pacific Medical Center
Contributor Information and Disclosures

Updated: Jan 12, 2010

Treatment

Medical Care

  • In general, no specific treatment exists for GSDs.
  • In some cases, diet therapy is helpful. Meticulous adherence to a dietary regimen may reduce liver size, prevent hypoglycemia, allow for reduction in symptoms, and allow for growth and development.
  • In 2000, Zingone and colleagues demonstrated the abolition of the murine clinical manifestations of Von Gierke disease with a recombinant adenoviral vector.7 These findings suggest that corrective gene therapy for GSDs may be possible in humans.
  • An encouraging study in 1999 by Bijvoet, Van Hirtum, and Kroos provides evidence of successful enzyme replacement for the mouse model of Pompe disease, which may lead to therapies for other enzyme deficiencies.8
  • For the infantile form, a recombinant enzyme replacement was approved by the FDA.
  • A high-protein diet may be beneficial in the noninfantile form.
  • Respiratory toilet is important in noninfantile cases.

Consultations

  • Consult a tertiary care center with access to a neurologist specializing in muscle disorders. This is helpful for determining differential diagnosis and the risk for other family members.
  • A genetic counselor can determine risk to future offspring.
  • Because of the supportive nature of care for infants with this disease, an expert in pediatric cardiology may be very beneficial.

Diet

A high-protein diet may provide increased muscle function in cases of weakness or exercise intolerance. In particular, a high-protein diet containing branched chain amino acids may slow or arrest disease progression.

Medication

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Enzyme, Replacement Therapy

Recombinant human enzyme alpha-glucosidase has been designated an orphan drug for use in Pompe disease.9

Strothotte et al assessed the effects of alglucosidase alfa replacement therapy on various stages of late-onset Pompe disease, using a series of tests on 44 patients with the condition.10 Replacement therapy was administered for 1 year (20 mg/kg IV q2wk), with tests performed at baseline and then every 3 months. Results from the 6-minute walk and modified Gowers' maneuver tests changed significantly, as did creatine kinase levels. Other test outcomes (eg, from serial arm function tests, timed 10 m walk tests, 4-stair climb tests) remained the same from baseline to endpoint. The patients experienced no serious adverse events. According to the authors, the data imply that the treatment of Pompe disease with alglucosidase alfa replacement can stabilize neuromuscular deficits and produce mild functional improvement in patients.


Alglucosidase alfa (Myozyme)

Recombinant human enzyme alpha-glucosidase (rhGAA) indicated as an orphan drug for treatment of Pompe disease. Replaces rhGAA, which is deficient or lacking in persons with Pompe disease. Alpha-glucosidase is essential for normal muscle development and function. Binds to mannose-6-phosphate receptors and then is transported into lysosomes; undergoes proteolytic cleavage that results in increased enzymatic activity and ability to cleave glycogen. Improves infant survival without requiring invasive ventilatory support compared with historical controls without treatment.

Adult

Data limited; administer as in pediatrics

Pediatric

20 mg/kg IV q2wk; initial infusion rate not to exceed 1 mg/kg/h; may increase infusion rate by 2 mg/kg/h q30min to a maximum of 7 mg/kg/h if tolerated

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Serious adverse effects reported include heart and lung failure; infusion-related reactions are common (51%) and include life-threatening anaphylaxis, shock, or respiratory or cardiac events (eg, bronchospasm, dyspnea, arrhythmias, hypotension, hypertension); medical support measures must be readily available; discontinue or temporarily stop infusion if reaction occurs; common adverse effects include pneumonia, respiratory failure and distress, infection, and fever

More on Glycogen Storage Disease, Type II (Pompe Disease)

Overview: Glycogen Storage Disease, Type II (Pompe Disease)
Differential Diagnoses & Workup: Glycogen Storage Disease, Type II (Pompe Disease)
Treatment & Medication: Glycogen Storage Disease, Type II (Pompe Disease)
Follow-up: Glycogen Storage Disease, Type II (Pompe Disease)
Multimedia: Glycogen Storage Disease, Type II (Pompe Disease)
References
Further Reading
[ CLOSE WINDOW ]

References

  1. Lukacs Z, Nieves Cobos P, Mengel E, et al. Diagnostic efficacy of the fluorometric determination of enzyme activity for Pompe disease from dried blood specimens compared with lymphocytes-possibility for newborn screening. J Inherit Metab Dis. Dec 23 2009;[Medline].

  2. Bijvoet AG, Van Hirtum H, Vermey M. Pathological features of glycogen storage disease type II highlighted in the knockout mouse model. J Pathol. Nov 1999;189(3):416-24. [Medline].

  3. Gort L, Coll MJ, Chabás A. Glycogen storage disease type II in Spanish patients: High frequency of c.1076-1G>C mutation. Mol Genet Metab. Sep-Oct 2007;92(1-2):183-7. [Medline].

  4. Martiniuk F, Chen A, Mack A. Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease. Am J Med Genet. Aug 27 1998;79(1):69-72. [Medline].

  5. Jones HN, Muller CW, Lin M, et al. Oropharyngeal dysphagia in infants and children with infantile Pompe disease. Dysphagia. Sep 10 2009;[Medline].

  6. Aminoff MJ. Electromyography in Clinical Practice. New York, NY: Churchill Livingstone; 1998.

  7. 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].

  8. Bijvoet AG, Van Hirtum H, Kroos MA. Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II. Hum Mol Genet. Nov 1999;8(12):2145-53. [Medline].

  9. Beck M. Alglucosidase alfa: Long term use in the treatment of patients with Pompe disease. Ther Clin Risk Manag. 2009;5:767-72. [Medline]. [Full Text].

  10. Strothotte S, Strigl-Pill N, Grunert B, et al. Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial. J Neurol. Jan 2010;257(1):91-7. [Medline].

  11. Phupong V, Shotelersuk V. Prenatal exclusion of Pompe disease by electron microscopy. Southeast Asian J Trop Med Public Health. Sep 2006;37(5):1021-4. [Medline].

  12. Chien YH, Lee NC, Thurberg BL, et al. Pompe disease in infants: improving the prognosis by newborn screening and early treatment. Pediatrics. Dec 2009;124(6):e1116-25. [Medline].

  13. Mah C, Cresawn KO, Fraites TJ Jr, Pacak CA, Lewis MA, Zolotukhin I. Sustained correction of glycogen storage disease type II using adeno-associated virus serotype 1 vectors. Gene Ther. Sep 2005;12(18):1405-9. [Medline].

  14. Amato AA. Acid maltase deficiency and related myopathies. Neurol Clin. Feb 2000;18(1):151-65. [Medline].

  15. Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. Jan 2000;105(1):e10. [Medline].

  16. Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen storage diseases. J Am Diet Assoc. Dec 1993;93(12):1423-30. [Medline].

  17. Hirshhorn R, Reuser A. Glycogen Storage Disease Type II: Acid alpha-Glucosidase (Acid Maltase) Deficiency. In: The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2001:3389-3420.

  18. Melvin JJ. Pompe's disease. Arch Neurol. Jan 2000;57(1):134-5. [Medline].

  19. Orho M, Bosshard NU, Buist NR. Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0. J Clin Invest. Aug 1 1998;102(3):507-15. [Medline].

  20. Sahin M, du Plessis AJ. Hydrocephalus associated with glycogen storage disease type II (Pompe's disease). Pediatr Neurol. Sep 1999;21(3):674-6. [Medline].

  21. Smit GP, Fernandes J, Leonard JV. The long-term outcome of patients with glycogen storage diseases. J Inherit Metab Dis. 1990;13(4):411-8. [Medline].

  22. Stevens AN, Iles RA, Morris PG. Detection of glycogen in a glycogen storage disease by 13C nuclear magnetic resonance. FEBS Lett. Dec 27 1982;150(2):489-93. [Medline].

  23. Sun B, Zhang H, Franco LM, Brown T, Bird A, Schneider A. Correction of glycogen storage disease type II by an adeno-associated virus vector containing a muscle-specific promoter. Mol Ther. Jun 2005;11(6):889-98. [Medline].

  24. Wolfsdorf JI, Holm IA, Weinstein DA. Glycogen storage diseases. Phenotypic, genetic, and biochemical characteristics, and therapy. Endocrinol Metab Clin North Am. Dec 1999;28(4):801-23. [Medline].

[ CLOSE WINDOW ]

Keywords

glycogen storage disease type II, Pompe disease, glycogen disease, glycogen storage disease, Pompe's disease, glucogenosis, lysosomal disease, acid maltase deficiency, glycogen accumulation

[ CLOSE WINDOW ]

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; Consulting Staff in Neurology, Department of Neurology, California Pacific Medical Center
Wayne E Anderson, DO is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Society of Law, Medicine & Ethics, California Medical Association, and San Francisco Medical Society
Disclosure: Cephalon Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; King Honoraria Consulting

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: eMedicine Salary Employment

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, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
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, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.