Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Myophosphorylase deficiency (glycogen storage disease V, McArdle disease)

J Lawrence Merritt II, MD
Section Editor
Sihoun Hahn, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS


Myophosphorylase (muscle phosphorylase) deficiency (MIM #232600), also known as McArdle disease, is the most common glycogen storage disease (GSD) affecting the muscle (figure 1) [1]. The GSDs are generally categorized by number according to the chronology of recognition of the responsible enzyme defect. As such, myophosphorylase deficiency is designated GSD V (table 1).

In myophosphorylase deficiency, glycogen is not properly broken down in muscle cells, interfering with their function. Patients usually present in adolescence or early adulthood with exercise intolerance, fatigue, myalgia, cramps, myoglobinuria, poor endurance, muscle swelling, and fixed weakness. A minimally invasive approach to the diagnosis of suspected myophosphorylase deficiency involves nonischemic forearm muscle exercise testing, although it is reasonable to perform genetic testing first in patients with clinical symptoms consistent with the diagnosis. Management includes avoidance of low-carbohydrate diets and low-to-moderate aerobic exercise.

Myophosphorylase deficiency (GSD V) is reviewed in detail here. Other GSDs and related disorders are reviewed separately. (See "Liver glycogen synthase deficiency (glycogen storage disease 0)" and "Glucose-6-phosphatase deficiency (glycogen storage disease I, von Gierke disease)" and "Lysosomal acid alpha-glucosidase deficiency (Pompe disease, glycogen storage disease II, acid maltase deficiency)" and "Lysosome-associated membrane protein 2 deficiency (glycogen storage disease IIb, Danon disease)" and "Glycogen debrancher deficiency (glycogen storage disease III)" and "Glycogen branching enzyme deficiency (glycogen storage disease IV, Andersen disease)" and "Liver phosphorylase deficiency (glycogen storage disease VI, Hers disease)" and "Phosphofructokinase deficiency (glycogen storage disease VII, Tarui disease)".)

A broader overview of GSD is also presented separately. (See "Overview of inherited disorders of glucose and glycogen metabolism".)


Myophosphorylase deficiency (McArdle disease, glycogen storage disease V [GSD V]) has an estimated prevalence of 1:167,000 in the Spanish population [2]. The prevalence in the Dallas-Fort Worth, Texas area was estimated to be 1:100,000 [3]. A positive family history for myophosphorylase deficiency is common and was seen in 53 percent of patients in one series [4].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Nov 24, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. McARDLE B. Myopathy due to a defect in muscle glycogen breakdown. Clin Sci 1951; 10:13.
  2. Lucia A, Ruiz JR, Santalla A, et al. Genotypic and phenotypic features of McArdle disease: insights from the Spanish national registry. J Neurol Neurosurg Psychiatry 2012; 83:322.
  3. Haller RG. Treatment of McArdle disease. Arch Neurol 2000; 57:923.
  4. DiMauro S, Bresolin N. Phosphorylase deficiency. In: Myology, Engel A, Banker B (Eds), McGraw-Hill, New York 1986. p.1585.
  5. Lebo RV, Gorin F, Fletterick RJ, et al. High-resolution chromosome sorting and DNA spot-blot analysis assign McArdle's syndrome to chromosome 11. Science 1984; 225:57.
  6. Nogales-Gadea G, Santalla A, Brull A, et al. The pathogenomics of McArdle disease--genes, enzymes, models, and therapeutic implications. J Inherit Metab Dis 2015; 38:221.
  7. Tsujino S, Shanske S, DiMauro S. Molecular genetic heterogeneity of myophosphorylase deficiency (McArdle's disease). N Engl J Med 1993; 329:241.
  8. Andersen ST, Dunø M, Schwartz M, Vissing J. Do carriers of PYGM mutations have symptoms of McArdle disease? Neurology 2006; 67:716.
  9. Schmidt B, Servidei S, Gabbai AA, et al. McArdle's disease in two generations: autosomal recessive transmission with manifesting heterozygote. Neurology 1987; 37:1558.
  10. el-Schahawi M, Tsujino S, Shanske S, DiMauro S. Diagnosis of McArdle's disease by molecular genetic analysis of blood. Neurology 1996; 47:579.
  11. Chui LA, Munsat TL. Dominant inheritance of McArdle syndrome. Arch Neurol 1976; 33:636.
  12. Papadimitriou A, Manta P, Divari R, et al. McArdle's disease: two clinical expressions in the same pedigree. J Neurol 1990; 237:267.
  13. Manfredi G, Silvestri G, Servidei S, et al. Manifesting heterozygotes in McArdle's disease: clinical, morphological and biochemical studies in a family. J Neurol Sci 1993; 115:91.
  14. Wu Y, Weber JL, Vladutiu GD, Tarnopolsky MA. Six novel mutations in the myophosphorylase gene in patients with McArdle disease and a family with pseudo-dominant inheritance pattern. Mol Genet Metab 2011; 104:587.
  15. Bartram C, Edwards RH, Clague J, Beynon RJ. McArdle's disease: a nonsense mutation in exon 1 of the muscle glycogen phosphorylase gene explains some but not all cases. Hum Mol Genet 1993; 2:1291.
  16. Bruno C, Lanzillo R, Biedi C, et al. Two new mutations in the myophosphorylase gene in Italian patients with McArdle's disease. Neuromuscul Disord 2002; 12:498.
  17. Tsujino S, Shanske S, Nonaka I, DiMauro S. The molecular genetic basis of myophosphorylase deficiency (McArdle's disease). Muscle Nerve Suppl 1995; 3:S23.
  18. Gámez J, Rubio JC, Martín MA, et al. Two novel mutations in the muscle glycogen phosphorylase gene in McArdle's disease. Muscle Nerve 2003; 28:380.
  19. Martín MA, Rubio JC, Wevers RA, et al. Molecular analysis of myophosphorylase deficiency in Dutch patients with McArdle's disease. Ann Hum Genet 2004; 68:17.
  20. Bruno C, Cassandrini D, Martinuzzi A, et al. McArdle disease: the mutation spectrum of PYGM in a large Italian cohort. Hum Mutat 2006; 27:718.
  21. Rubio JC, Lucia A, Fernández-Cadenas I, et al. Novel mutation in the PYGM gene resulting in McArdle disease. Arch Neurol 2006; 63:1782.
  22. Petrou P, Pantzaris M, Dionysiou M, et al. Minimally symptomatic mcardle disease, expanding the genotype-phenotype spectrum. Muscle Nerve 2015; 52:891.
  23. Rubio JC, Garcia-Consuegra I, Nogales-Gadea G, et al. A proposed molecular diagnostic flowchart for myophosphorylase deficiency (McArdle disease) in blood samples from Spanish patients. Hum Mutat 2007; 28:203.
  24. Sugie H, Sugie Y, Ito M, et al. Genetic analysis of Japanese patients with myophosphorylase deficiency (McArdle's disease): single-codon deletion in exon 17 is the predominant mutation. Clin Chim Acta 1995; 236:81.
  25. Vissing J, Duno M, Schwartz M, Haller RG. Splice mutations preserve myophosphorylase activity that ameliorates the phenotype in McArdle disease. Brain 2009; 132:1545.
  26. Dimaur S, Andreu AL, Bruno C, Hadjigeorgiou GM. Myophosphorylase deficiency (glycogenosis type V; McArdle disease). Curr Mol Med 2002; 2:189.
  27. Martín MA, Rubio JC, Buchbinder J, et al. Molecular heterogeneity of myophosphorylase deficiency (McArdle's disease): a genotype-phenotype correlation study. Ann Neurol 2001; 50:574.
  28. Martinuzzi A, Sartori E, Fanin M, et al. Phenotype modulators in myophosphorylase deficiency. Ann Neurol 2003; 53:497.
  29. Rubio JC, Gómez-Gallego F, Santiago C, et al. Genotype modulators of clinical severity in McArdle disease. Neurosci Lett 2007; 422:217.
  30. DiMauro S, Hartlage PL. Fatal infantile form of muscle phosphorylase deficiency. Neurology 1978; 28:1124.
  31. Milstein JM, Herron TM, Haas JE. Fatal infantile muscle phosphorylase deficiency. J Child Neurol 1989; 4:186.
  32. Ito Y, Saito K, Shishikura K, et al. A 1-year-old infant with McArdle disease associated with hyper-creatine kinase-emia during febrile episodes. Brain Dev 2003; 25:438.
  33. Ørngreen MC, Jeppesen TD, Andersen ST, et al. Fat metabolism during exercise in patients with McArdle disease. Neurology 2009; 72:718.
  34. Nadaj-Pakleza AA, Vincitorio CM, Laforêt P, et al. Permanent muscle weakness in McArdle disease. Muscle Nerve 2009; 40:350.
  35. Rommel O, Kley RA, Dekomien G, et al. Muscle pain in myophosphorylase deficiency (McArdle's disease): the role of gender, genotype, and pain-related coping. Pain 2006; 124:295.
  36. Argov Z, Bank WJ. Phosphorus magnetic resonance spectroscopy (31P MRS) in neuromuscular disorders. Ann Neurol 1991; 30:90.
  37. Kazemi-Esfarjani P, Skomorowska E, Jensen TD, et al. A nonischemic forearm exercise test for McArdle disease. Ann Neurol 2002; 52:153.
  38. Lindner A, Reichert N, Eichhorn M, Zierz S. Acute compartment syndrome after forearm ischemic work test in a patient with McArdle's disease. Neurology 2001; 56:1779.
  39. Servidei S, Shanske S, Zeviani M, et al. McArdle's disease: biochemical and molecular genetic studies. Ann Neurol 1988; 24:774.
  40. McConchie SM, Coakley J, Edwards RH, Beynon RJ. Molecular heterogeneity in McArdle's disease. Biochim Biophys Acta 1990; 1096:26.
  41. Bruno C, Hays AP, DiMauro S. Glycogen storage diseases of muscle. In: Neuromuscular disorders of infancy, childhood, and adolescence: A clinician's approach, Jones HR Jr, De Vivo DC, Darras BT (Eds), Butterworth Heinemann, Philadelphia 2003. p.813.
  42. Quinlivan R, Martinuzzi A, Schoser B. Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V). Cochrane Database Syst Rev 2014; :CD003458.
  43. Martinuzzi A, Liava A, Trevisi E, et al. Randomized, placebo-controlled, double-blind pilot trial of ramipril in McArdle's disease. Muscle Nerve 2008; 37:350.
  44. Andersen ST, Vissing J. Carbohydrate- and protein-rich diets in McArdle disease: effects on exercise capacity. J Neurol Neurosurg Psychiatry 2008; 79:1359.
  45. Vissing J, Haller RG. The effect of oral sucrose on exercise tolerance in patients with McArdle's disease. N Engl J Med 2003; 349:2503.
  46. Andersen ST, Haller RG, Vissing J. Effect of oral sucrose shortly before exercise on work capacity in McArdle disease. Arch Neurol 2008; 65:786.
  47. Pérez M, Maté-Muñoz JL, Foster C, et al. Exercise capacity in a child with McArdle disease. J Child Neurol 2007; 22:880.
  48. Haller RG, Wyrick P, Taivassalo T, Vissing J. Aerobic conditioning: an effective therapy in McArdle's disease. Ann Neurol 2006; 59:922.
  49. Pérez M, Foster C, González-Freire M, et al. One-year follow-up in a child with McArdle disease: exercise is medicine. Pediatr Neurol 2008; 38:133.
  50. Quinlivan R, Vissing J, Hilton-Jones D, Buckley J. Physical training for McArdle disease. Cochrane Database Syst Rev 2011; :CD007931.
  51. Maté-Muñoz JL, Moran M, Pérez M, et al. Favorable responses to acute and chronic exercise in McArdle patients. Clin J Sport Med 2007; 17:297.
  52. Vorgerd M, Grehl T, Jager M, et al. Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial. Arch Neurol 2000; 57:956.
  53. Vorgerd M, Zange J, Kley R, et al. Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study. Arch Neurol 2002; 59:97.
  54. GeneReviews topic on Glycogen Storage Disease Type V. http://www.ncbi.nlm.nih.gov.ezp-prod1.hul.harvard.edu/books/NBK1344/.
  55. Lobato EB, Janelle GM, Urdaneta F, Malias MA. Noncardiogenic pulmonary edema and rhabdomyolsis after protamine administration in a patient with unrecognized McArdle's disease. Anesthesiology 1999; 91:303.
  56. Bollig G, Mohr S, Raeder J. McArdle's disease and anaesthesia: case reports. Review of potential problems and association with malignant hyperthermia. Acta Anaesthesiol Scand 2005; 49:1077.
  57. Livingstone C, Al Riyami S, Wilkins P, Ferns GA. McArdle's disease diagnosed following statin-induced myositis. Ann Clin Biochem 2004; 41:338.
  58. Vladutiu GD, Simmons Z, Isackson PJ, et al. Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle Nerve 2006; 34:153.
  59. Lorenzoni PJ, Silvado CE, Scola RH, et al. McArdle disease with rhabdomyolysis induced by rosuvastatin: case report. Arq Neuropsiquiatr 2007; 65:834.
  60. Vladutiu GD. Genetic predisposition to statin myopathy. Curr Opin Rheumatol 2008; 20:648.
  61. Quinlivan R, Buckley J, James M, et al. McArdle disease: a clinical review. J Neurol Neurosurg Psychiatry 2010; 81:1182.