Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Genetics of Glycogen-Storage Disease Type VII Workup

  • Author: Lynne Ierardi-Curto, MD, PhD; Chief Editor: Maria Descartes, MD  more...
 
Updated: Oct 03, 2013
 

Laboratory Studies

See the list below:

  • Serum creatine kinase (CK) values are usually increased in patients with Tarui disease (glycogen-storage disease type VII).
  • Lactic acid does not increase following exercise.
  • Bilirubin levels may be elevated.
  • Reticulocyte count and reticulocyte distribution width (RDW) may be increased.
  • Urinalysis may reveal myoglobinuria, especially after exercise.
Next

Imaging Studies

Brain imaging scans in patients with the infantile-onset subtype may show cortical atrophy and ventricular dilatation.

Phosphorus-31 nuclear magnetic resonance spectroscopy (31 P-NMR S) of calf muscle using a 4.7-Tesla MRI may be useful in making this diagnosis. During exercise, glycolytic intermediates accumulate as phosphorylated monoesters that are pathognomonic of Tarui disease. This study also shows the absence of lactic acid production.[14]

Previous
Next

Other Tests

Electromyography (EMG) may reveal small-motor potentials of short duration consistent with myopathic changes.

Echocardiography may reveal valvular thickening, and ECG may reveal an arrhythmia.

The ischemic forearm test is an important tool for the diagnosis of metabolic myopathies. The test examines the metabolic pathways that provide energy for muscle function during anaerobic exercise.

First, a blood pressure cuff is placed on the patient's arm and is inflated above systolic pressure.

The patient is then instructed to repetitively grasp an object (once or twice per second) for 2-3 minutes.

Blood samples for creatine kinase, ammonia, and lactate and urine samples for myoglobin analysis are immediately obtained before and 5 minutes, 10 minutes, and 20 minutes after inflating the cuff.

Healthy patients have an increase in lactate levels of at least 5-10 mg/dL and an increase in ammonia levels of at least 100 mcg/dL, with return to baseline. If neither level increases, the exercise was not strenuous enough, and the test results are not valid.

Increased lactate at rest (before exercise) is evidence of mitochondrial myopathy.

Failure of ammonia to increase with lactate is evidence of myoadenylate deaminase deficiency. The failure of lactate to increase with ammonia is evidence of a glycogen-storage disease that results in blockage of a carbohydrate metabolic pathway.

Positive ischemic forearm test results may occur in patients with Tarui disease, Cori disease (glycogen-storage disease type III), and McArdle disease (glycogen-storage disease type V).

The absence of a spontaneous second wind in a patient with suspected Tarui disease can be studied by an exercise test after an overnight fast. Continuous cycling for 15-20 minutes on a bicycle ergometer is maintained at a constant workload. Peak exercise capacity is determined after 6-8 minutes of exercise and again at 25-30 minutes of exercise. Heart rate is monitored continuously, and perceived exertion (Borg scale) is recorded during each minute of exercise. A spontaneous second wind is accompanied by decreased heart rate, perceived exertion, and increased oxygen consumption. Only patients with McArdle disease (glycogen-storage disease type V) exhibit a spontaneous second wind. A spontaneous second wind does not occur in patients with Tarui disease (glycogen-storage disease type VII), phosphoglycerate kinase deficiency, phosphoglycerate mutase deficiency, and certain mitochondrial disorders[15] .

Glucose or sucrose intake before exercise will exacerbate the muscle symptoms in patients with Tarui disease. Tirty minutes before an exercise test, a beverage containing 75 grams of sucrose is ingested or a glucose infusion of 6 ml per minute is begun. Carbohydrate intake increases the symptoms of exercise intolerance in Tarui disease. In contrast, carbohydrate decreases the symptoms of exercise intolerance in McArdle disease (glycogen-storage disease type V) and has no effect on phosphoglycerate mutase deficiency[15] .

Demonstration of decreased phosphofructokinase (PFK) enzyme activity in muscle tissue is considered definitive biochemical diagnosis of Tarui disease.

The demonstration of homozygous or compound heterozygous mutations in the PFKM gene by sequence analysis is considered definitive molecular diagnosis of Tarui disease. Targeted mutation analysis may be considered in Ashkenazi Jewish patients and when a familial mutation has been identified.

Previous
Next

Procedures

See the list below:

  • Muscle biopsy is necessary for microscopic and biochemical assay of PFK activity.
Previous
Next

Histologic Findings

See the list below:

  • Glycogen accumulates between myofibrils under the sarcolemma, as in McArdle disease. Muscle glycogen content typically is greater than 1.5 g per 100 g wet muscle weight.
  • An abnormal polysaccharide, unique to Tarui disease, may also be found, especially in older patients. This polysaccharide is periodic acid-Schiff (PAS) positive but is not digested by diastase.
  • Nonspecific myopathic changes may also be observed.
  • In infantile-onset Tarui disease, little histological evidence of glycogen accumulation may be evident, but measured glycogen is typically greater than twice the normal amount.
Previous
 
 
Contributor Information and Disclosures
Author

Lynne Ierardi-Curto, MD, PhD Attending Physician, Division of Metabolism, Children's Hospital of Philadelphia

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.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Cydney L Fenton, MD, FAAP, and Melissa Wasserstein, MD, to the development and writing of this article.

References
  1. Tarui S, Okuno G, Ikura Y, et al. Phosphofructokinase deficiency in skeletal muscle: a new type of glycogenosis. Biochem Biophys Res Commun. 1965 May 3. 19:517-23. [Medline].

  2. Toscano A, Musumeci O. Tarui disease and distal glycogenoses: clinical and genetic update. Acta Myol. 2007 Oct. 26(2):105-7. [Medline].

  3. Nakajima H, Raben N, Hamaguchi T, Yamasaki T. Phosphofructokinase deficiency; past, present and future. Curr Mol Med. 2002 Mar. 2(2):197-212. [Medline].

  4. Haller RG, Lewis SF. Glucose-induced exertional fatigue in muscle phosphofructokinase deficiency. N Engl J Med. 1991 Feb 7. 324(6):364-9. [Medline].

  5. Ono A, Kuwajima M, Kono N, Mineo I, Nakagawa C, Tarui S, et al. Glucose infusion paradoxically accelerates degradation of adenine nucleotide in working muscle of patients with glycogen storage disease type VII. Neurology. 1995 Jan. 45(1):161-4. [Medline].

  6. Vissing J, Haller RG. The effect of oral sucrose on exercise tolerance in patients with McArdle's disease. N Engl J Med. 2003 Dec 25. 349(26):2503-9. [Medline].

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

  8. Di Mauro S. Muscle glycogenoses: an overview. Acta Myol. 2007 Jul. 26(1):35-41. [Medline]. [Full Text].

  9. 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].

  10. Amit R, Bashan N, Abarbanel JM, et al. Fatal familial infantile glycogen storage disease: multisystem phosphofructokinase deficiency. Muscle Nerve. 1992. 14:455-458. [Medline].

  11. 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].

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

  13. Raben N, Sherman JB. Mutations in muscle phosphofructokinase gene. Hum Mutat. 1995. 6(1):1-6. [Medline].

  14. Drouet A, Zagnoli F, Fassier T, et al. [Exercise-induced muscle pain due to phosphofrutokinase deficiency: Diagnostic contribution of metabolic explorations (exercise tests, 31P-nuclear magnetic resonance spectroscopy).]. Rev Neurol (Paris). 2013 Aug 30. [Medline].

  15. Berardo A, DiMauro S, Hirano M. A diagnostic algorithm for metabolic myopathies. Curr Neurol Neurosci Rep. 2010 Mar. 10(2):118-26. [Medline]. [Full Text].

  16. Chen YT. Glycogen storage diseases. Scriver CR, Sly WS, Childs B, Beaudet AL, Valle D, Kinzler KW, Vogelstein B. The Metabolic and Molecular Bases of Inherited Disease. 8th. New York, NY: McGraw-Hill Professionals; 2001. 1521-51.

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.