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Type VII Glycogen Storage Disease

  • Author: Wayne E Anderson, DO, FAHS, FAAN; Chief Editor: George T Griffing, MD  more...
 
Updated: Aug 25, 2014
 

Background

A glycogen storage disease (GSD) is the result of an enzyme defect. These enzymes normally catalyze reactions that ultimately convert glycogen compounds to glucose. Enzyme deficiency results in glycogen accumulation in tissues. In many cases, the defect has systemic consequences, but in some cases, the defect is limited to specific tissues. Most patients experience muscle symptoms, such as weakness and cramps, although certain GSDs manifest as specific syndromes, such as hypoglycemic seizures or cardiomegaly.

The following list contains a quick reference for 8 of the GSD types:

  • 0 - Glycogen synthase deficiency
  • Ia - Glucose-6-phosphatase deficiency (von Gierke disease)
  • II - Acid maltase deficiency (Pompe disease)
  • III - Debranching enzyme deficiency (Forbes-Cori disease)
  • IV - Transglucosidase deficiency (Andersen disease, amylopectinosis)
  • V - Myophosphorylase deficiency (McArdle disease)
  • VI - Phosphorylase deficiency (Hers disease)
  • VII - Phosphofructokinase deficiency (Tarui disease)

The chart below demonstrates where various forms of GSD affect the metabolic carbohydrate pathways.

Metabolic pathways of carbohydrates. Metabolic pathways of carbohydrates.

Although at least 14 unique GSDs are discussed in the literature, the 4 that cause clinically significant muscle weakness are Pompe disease (GSD type II, acid maltase deficiency), Cori disease (GSD type III, debranching enzyme deficiency), McArdle disease (GSD type V, myophosphorylase deficiency), and Tarui disease (GSD type VII, phosphofructokinase deficiency), which is often misspelled as Tauri disease. One form, von Gierke disease (GSD type Ia, glucose-6-phosphatase deficiency), causes clinically significant end-organ disease with significant morbidity. The remaining GSDs are not benign but are less clinically significant; therefore, the physician should consider the aforementioned GSDs when initially entertaining the diagnosis of a GSD. Interestingly, GSD type 0 also is described, which is due to defective glycogen synthase.

These inherited enzyme defects usually present in childhood, although some, such as McArdle disease and Pompe disease, have separate adult-onset forms. In general, GSDs are inherited as autosomal recessive conditions. Several different mutations have been reported for each disorder.

Unfortunately, no specific treatment or cure exists, although diet therapy may be highly effective at reducing clinical manifestations. In some cases, liver transplantation may abolish biochemical abnormalities. Active research continues.

Diagnosis depends on findings from muscle biopsy, electromyography, ischemic forearm testing, creatine kinase testing, patient history, and physical examination. Biochemical assay for enzyme activity is the method of definitive diagnosis.

Phosphofructokinase catalyzes the rate-limiting step in glycolysis. Phosphofructokinase deficiency leads to muscle pain and exercise-induced fatigue and weakness. Tarui disease resolves with rest, and, although no specific treatment exists, the condition may not progress to severe disability.

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Pathophysiology

With an enzyme defect, carbohydrate metabolic pathways are blocked and excess glycogen accumulates in affected tissues. Each GSD represents a specific enzyme defect, and each enzyme is in specific or most body tissues. Phosphofructokinase catalyzes the rate-limiting step in glycolysis. Enzyme deficiency decreases the rate of conversion of fructose-6-phosphate to fructose-1,6-diphosphate. Phosphofructokinase is found in muscle tissue and red blood cells.

Tarui disease is an autosomal recessive condition.

Garcia et al investigated the effects of phosphofructokinase deficiency in tissue other than skeletal muscle on the pathogenesis of GSD type VII.[1] In a study of phosphofructokinase-deficient mice, the authors found that because the animals' erythrocytes retained only 50% of their phosphofructokinase activity, severe hemolysis, significant decreases in 2,3-bisphosphoglycerate levels (impairing the extraction of oxygen from hemoglobin), and compensatory reticulocytosis and splenomegaly occurred. Reduced levels of cardiac phosphofructokinase activity were found as well, which, combined with the other hematologic changes, led to the development of cardiac hypertrophy.

Madhoun et al reported a unique case of a man with phosphofructokinase deficiency who also presented with portal and mesenteric vein thrombosis.[2]

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Epidemiology

Frequency

International

Herling and colleagues studied the incidence and frequency of inherited metabolic conditions in British Columbia. GSDs are found in 2.3 children per 100,000 births per year.

Mortality/Morbidity

As in McArdle disease, immediate morbidity arises from exercise intolerance.

Unlike in McArdle disease, Haller and Vissing found no consistent second wind phenomenon in GSD VII.[3]

Race

The disease appears to be prevalent among people of Ashkenazi Jewish descent.

Age

In general, GSDs present in childhood. Later onset correlates with a less severe form. Consider Pompe disease if onset is in infancy.

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Contributor Information and Disclosures
Author

Wayne E Anderson, DO, FAHS, FAAN Assistant Professor of Internal Medicine/Neurology, College of Osteopathic Medicine of the Pacific Western University of Health Sciences; Clinical Faculty in Family Medicine, Touro University College of Osteopathic Medicine; Clinical Instructor, Departments of Neurology and Pain Management, California Pacific Medical Center

Wayne E Anderson, DO, FAHS, FAAN is a member of the following medical societies: California Medical Association, American Headache Society, San Francisco Medical Society, San Francisco Medical Society, International Headache Society, California Neurology Society, San Francisco Neurological Society, American Academy of Neurology, California Medical Association

Disclosure: Received honoraria from Teva for speaking and teaching; Received grant/research funds from Allergan for other; Received honoraria from Insys for speaking and teaching; Received honoraria from DepoMed for speaking and teaching.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

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, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus 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, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

David M Klachko, MD, MEd Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Missouri-Columbia School of Medicine

David M Klachko, MD, MEd is a member of the following medical societies: Alpha Omega Alpha, Missouri State Medical Association, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, Endocrine Society, Sigma Xi

Disclosure: Nothing to disclose.

References
  1. Garcia M, Pujol A, Ruzo A, et al. Phosphofructo-1-kinase deficiency leads to a severe cardiac and hematological disorder in addition to skeletal muscle glycogenosis. PLoS Genet. 2009 Aug. 5(8):e1000615. [Medline]. [Full Text].

  2. Madhoun MF, Maple JT, Comp PC. Phosphofructokinase deficiency and portal and mesenteric vein thrombosis. Am J Med Sci. 2011 May. 341(5):417-9. [Medline].

  3. Haller RG, Vissing J. No spontaneous second wind in muscle phosphofructokinase deficiency. Neurology. 2004 Jan 13. 62(1):82-6. [Medline].

  4. Haller RG, Vissing J. No spontaneous second wind in muscle phosphofructokinase deficiency. Neurology. 2004 Jan 13. 62(1):82-6. [Medline].

  5. Exantus J, Ranchin B, Dubourg L, et al. Acute renal failure in a patient with phosphofructokinase deficiency. Pediatr Nephrol. 2004 Jan. 19(1):111-3. [Medline].

  6. Finsterer J, Stollberger C, Kopsa W. Neurologic and cardiac progression of glycogenosis type VII over an eight-year period. South Med J. 2002 Dec. 95(12):1436-40. [Medline].

  7. Finsterer J, Stollberger C. Progressive mitral valve thickening and progressive muscle cramps as manifestations of glycogenosis VII (Tarui's Disease). Cardiology. 2008. 110(4):238-40. [Medline].

  8. Musumeci O, Bruno C, Mongini T, Rodolico C, Aguennouz M, Barca E, et al. Clinical features and new molecular findings in muscle phosphofructokinase deficiency (GSD type VII). Neuromuscul Disord. 2012 Apr. 22(4):325-30. [Medline].

  9. Zingone A, Hiraiwa H, Pan CJ. Correction of glycogen storage disease type 1a in a mouse model by gene therapy. J Biol Chem. 2000 Jan 14. 275(2):828-32. [Medline].

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

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

  12. Aminoff MJ, ed. Electromyography in Clinical Practice. 3rd ed. New York, NY: Churchill Livingstone; 1998.

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

  14. Chen Y. Glycogen Storage Diseases. Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2000. Vol 1: 1539-40.

  15. DiMauro S, Bruno C. Glycogen storage diseases of muscle. Curr Opin Neurol. 1998 Oct. 11(5):477-84. [Medline].

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

  17. Lin HC, Young C, Wang PJ. Muscle phosphofructokinase deficiency (Tarui''s disease): report of a case. J Formos Med Assoc. 1999 Mar. 98(3):205-8. [Medline].

  18. Raben N, Sherman JB, Adams E. Various classes of mutations in patients with phosphofructokinase deficiency (Tarui''s disease). Muscle Nerve. 1995. 3:S35-8. [Medline].

  19. 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].

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

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

 
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