Abstract
This review highlights recent advances in our understanding of McArdle’s disease, including the mechanisms involved in the regulation of the clinical phenotype. The latest molecular genetic studies have demonstrated the genetic heterogeneity of the disorder, with more than 65 mutations identified to date. There is not a specific treatment for McArdle’s disease, but some nutritional treatments in combination with aerobic conditioning could improve the quality of life in most patients.
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References and Recommended Reading
McArdle B: Myopathy due to a defect in muscle glycogen breakdown. Clin Sci 1951, 10:13–33.
DiMauro S, Andreu AL, Bruno C, et al.: Myophosphorylase Deficiency (Glycogenosis Type V; McArdle Disease). Curr Mol Med 2002, 2:189–196.
Bruno C, Hays AP, DiMauro S: Glycogen storage diseases of muscle. In Neuromuscular Disorders of Infancy, Childhood, and Adolescence. Edited by Jones HR, De Vivo DC, Darras BT. Amsterdam: Butterworth-Heinemann; 2002:813–832.
Martinuzzi A, Vergani L, Carrozzo R, et al.: Expression of muscle-type phosphorylase in innervated and aneural cultured muscle of patients with myophosphorylase deficiency. J Clin Invest 1993, 92:1774–1780.
Browner MF, Fletterick RJ: Phosphorylase: a biological transducer. Trends Biochem Sci 1992, 17:66–71.
DiMauro S, Tsujino S: Nonlysosomal glycogenoses. In Myology. Edited by Engel AG, Franzini-Amstrong C. New York: McGraw-Hill; 1995:1554–1576.
Braakhekke JP, de Bruin MI, Stegeman DF, et al.: The second wind phenomenon in McArdle’s disease. Brain 1986, 109:1087–1101.
Haller RG, Vissing J: Spontaneous “second wind” and glucose-induced second “second wind” in McArdle disease: oxidative mechanisms. Arch Neurol 2002, 59:1395–1402.
Martinuzzi A, Tsujino S, Vergani L, et al.: Molecular characterization of myophosphorylase deficiency in a group of patients from northern Italy. J Neurol Sci 1996, 137:14–19.
Tsujino S, Shanske S, DiMauro S: Molecular genetic heterogeneity of myophosphorylase deficiency (McArdle’s disease). N Engl J Med 1993, 329:241–245.
Hadjigeorgiou GM, Sadeh M, Musumeci O, et al.: Molecular genetic study of myophosphorylase deficiency (McArdle’s disease) in two Yemenite-Jewish families. Neuromuscul Disord 2002, 12:824–827.
Isackson PJ, Tarnopolsky M, Vladutiu GD: A novel mutation in the PYGM gene in a family with pseudo-dominant transmission of McArdle disease. Mol Genet Metab 2005, 85:239–242.
Andreu AL, Bruno C, Tamburino L, et al.: A new mutation in the myophosphorylase gene (Asn684Tyr) in a Spanish patient with McArdle’s disease. Neuromuscul Disord 1999, 9:171–173.
Paradas C, Fernandez-Cadenas I, Gallardo E, et al.: Variable presentation of the clinical phenotype of McArdle’s disease in a kindred harbouring a novel compound genotype in the muscle glycogen phosphorylase gene. Neurosci Lett 2005, 391:28–31.
Voduc N, Webb KA, D’Arsigny C, et al.: McArdle’s disease presenting as unexplained dyspnea in a young woman. Can Respir J 2004, 11:163–167.
Martinuzzi A, Sartori E, Fanin M, et al.: Phenotype modulators in myophosphorylase deficiency. Ann Neurol 2003, 53:497–502.
DiMauro S, Hartlage PL: Fatal infantile form of muscle phosphorylase deficiency. Neurology 1978, 28:1124–1129.
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.
Lindner A, Reichert N, Eichhorn M, et al.: Acute compartment syndrome after forearm ischemic work test in a patient with McArdle’s disease. Neurology 2001, 56:1779–1780.
Kazemi-Esfarjani P, Skomorowska E, Jensen TD, et al.: A nonischemic forearm exercise test for McArdle disease. Ann Neurol 2002, 52:153–159.
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, 225:57–59.
Bartram C, Edwards RH, Clague J, et al.: 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, 2:1291–1293.
den Dunen JT, Antonarakis SE: Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 2000, 15:7–12.
den Dunnen JT, Paalman MH: Standardizing mutation nomenclature: why bother?. Hum Mutat 2003, 22:181–182.
Martin MA, Rubio JC, Buchbinder J, et al.: Molecular heterogeneity of myophosphorylase deficiency (McArdle’s disease): a genotype-phenotype correlation study. Ann Neurol 2001, 50:574–581.
Bruno C, Tamburino L, Kawashima N, et al.: A nonsense mutation in the myophosphorylase gene in a Japanese family with McArdle’s disease. Neuromuscul Disord 1999, 9:34–37.
Bruno C, Lofberg M, Tamburino L, et al.: Molecular characterization of McArdle’s disease in two large Finnish families. J Neurol Sci 1999, 165:121–125.
Bartram C, Edwards RH, Clague J, et al.: McArdle’s disease: a rare frameshift mutation in exon 1 of the muscle glycogen phosphorylase gene. Biochim Biophys Acta 1994, 1226:341–343.
el-Schahawi M, Tsujino S, Shanske S, et al.: Diagnosis of McArdle’s disease by molecular genetic analysis of blood. Neurology 1996, 47:579–580.
Vorgerd M, Kubisch C, Burwinkel B, et al.: Mutation analysis in myophosphorylase deficiency (McArdle’s disease). Ann Neurol 1998, 43:326–331.
Bruno C, DiMauro S, Lombes A, et al.: Molecular study in a large series of French patients with McArdle’s disease. J Neurol 2000, 274:120–121.
Martin MA, Rubio JC, Wevers RA, et al.: Molecular analysis of myophosphorylase deficiency in Dutch patients with McArdle’s disease. Ann Hum Genet 2004, 68:17–22.
Hadjigeorgiou GM, Papadimitriou A, Musumeci O, et al.: A new stop codon mutation (Y52X) in the myophosphorylase gene in a Greek patient with McArdle’s disease. J Neurol Sci 2002, 194:83–86.
Quintans B, Sanchez-Andrade A, Tejeira S, et al.: A new rare mutation (691delCC/InsAAA) in exon 17 of the PYGM gene causing McArdle disease. Arch Neurol 2004, 61:1108–1110.
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, 236:81–86.
Deschauer M, Opalka JR, Lindner A, et al.: A novel nonsense mutation (R269X) in the myophosphorylase gene in a patient with McArdle disease. Mol Genet Metab 2001, 74:489–491.
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, 12:498–500.
Tsujino S, Shanske S, Martinuzzi A: Two novel missense mutations (E654K, L396P) in Caucasian patients with myophosphorylase deficiency (McArdle’s disease). Hum Mutat 1995, 6:276–277.
Tsujino S, Shanske S, Nonaka I, et al.: Three new mutations in patients with myophosphorylase deficiency (McArdle disease). Am J Hum Genet 1994, 54:44–52.
Iyengar S, Kalinsky H, Weiss S, et al.: Homozygosity by descent for a rare mutation in the myophosphorylase gene is associated with variable phenotypes in a Druze family with McArdle disease. J Med Genet 1997, 34:391–394.
Kubisch C, Wicklein EM, Jentsch TJ: Molecular diagnosis of McArdle disease: revised genomic structure of the myophosphorylase gene and identification of a novel mutation. Hum Mutat 1998, 12:27–32.
Martin MA, Rubio JC, Garcia A, et al.: Resolution of a mispaired secondary structure intermediate could account for a novel micro-insertion/deletion (387 insA/del 8 bp) in the PYGM gene causing McArdle’s disease. Clin Genet 2001, 59:48–51.
Fernandez-Cadenas I, Andreu AL, Gamez J, et al.: Splicing mosaic of the myophosphorylase gene due to a silent mutation in McArdle disease. Neurology 2003, 61:1432–1434.
Quinlivan R, Beynon RJ: Pharmacological and nutritional treatment for McArdle’s disease (Glycogen Storage Disease type V). Cochrane Database Syst Rev 2004, CD003458.
Slonim AE, Goans PJ: Myopathy in McArdle’s syndrome. Improvement with a high-protein diet. N Engl J Med 1985, 312:355–359.
Jensen KE, Jakobsen J, Thomsen C, et al.: Improved energy kinetics following high protein diet in McArdle’s syndrome. A 31P magnetic resonance spectroscopy study. Acta Neurol Scand 1990, 81:499–503.
MacLean D, Vissing J, Vissing SF, et al.: Oral branchedchain amino acids do not improve exercise capacity in McArdle disease. Neurology 1998, 51:1456–1459.
Haller RG, Wyrick P, Cavender D, et al.: Neurology 1998, 50:A369.
Haller RG: Treatment of McArdle disease. Arch Neurol 2000, 57:923–924.
Phoenix J, Hopkins P, Bartram C, et al.: Effect of vitamin B6 supplementation in McArdle’s disease: a strategic case study. Neuromuscul Disord 1998, 8:210–212.
Vorgerd M, Grehl T, Jager M, et al.: Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial. Arch Neurol 2000, 57:956–963.
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, 59:97–101.
Pari G, Crerar MM, Nalbantoglu J, et al.: Myophosphorylase gene transfer in McArdle’s disease myoblasts in vitro. Neurology 1999, 53:1352–1354.
Vissing J, Haller RG: The effect of oral sucrose on exercise tolerance in patients with McArdle’s disease. N Engl J Med 2003, 349:2503–2509.
Amato AA: Sweet success—a treatment for McArdle’s disease. N Engl J Med 2003, 349:2481–2482.
Tsujino S, Shanske S, Nonaka I, et al.: The molecular genetic basis of myophosphorylase deficiency (McArdle’s disease). Muscle Nerve 1995, 3:S23–S27.
Deschauer M, Hertel K, Zierz S: Two novel mutations in the myophosphorylase gene in a patient with McArdle disease. Muscle Nerve 2003, 27:105–107.
Gamez J, Fernandez R, Bruno C, et al.: A new mutation in the regulatory domain of the myophosphorylase gene affecting protein dimer contact. Muscle Nerve 1999, 22:1136–1138.
Martin MA, Rubio JC, Campos Y, et al.: Two homozygous mutations (R193W and 794/795 delAA) in the myophosphorylase gene in a patient with McArdle’s disease. Hum Mutat 2000, 15:294.
Mancuso M, Filosto M, Tsujino S, et al.: Muscle glycogenosis and mitochondrial hepatopathy in an infant with mutations in both the myophosphorylase and deoxyguanosine kinase genes. Arch Neurol 2003, 60:1445–1447.
Rubio JC, Martin MA, Campos Y, et al.: A missense mutation T487N in the myophosphorylase gene in a Spanish patient with McArdle’s disease. Neuromuscul Disord 2000, 10:138–140.
Tsujino S, Shanske S, Goto Y, et al.: Two mutations, one novel and one frequently observed, in Japanese patients with McArdle’s disease. Hum Mol Genet 1994, 3:1005–1006.
Gamez J, Rubio JC, Martin MA, et al.: Two novel mutations in the muscle glycogen phosphorylase gene in McArdle’s disease. Muscle Nerve 2003, 28:380–382.
Martin MA, Rubio JC, Campos Y, et al.: A homozygous missense mutation (A659D) in the myophosphorylase gene in a Spanish patient with McArdle’s disease. Neuromuscul Disord 2000, 10:447–449.
Martinuzzi A, Schievano G, Nascimbeni A, et al.: McArdle’s disease. The unsolved mystery of the reappearing enzyme. Am J Pathol 1999, 154:1893–1897.
Rubio JC, Martin MA, Campos Y, et al.: A missense mutation W797R in the myophosphorylase gene in a Spanish patient with McArdle’s disease. Muscle Nerve 2000, 23:129–131.
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Nogales-Gadea, G., Arenas, J. & Andreu, A.L. Molecular genetics of McArdle’s disease. Curr Neurol Neurosci Rep 7, 84–92 (2007). https://doi.org/10.1007/s11910-007-0026-2
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DOI: https://doi.org/10.1007/s11910-007-0026-2