Neuromuscular, cognitive and metabolic implications of McArdle Syndrome: a global overview

  • Authors

    • Lucas Vieira Ceará State University
    • Rafaela Soares Ceará State University
    • Stela Felipe Ceará State University
    • Felipe Moura
    • Christina Pacheco Ceará State University
    • Vânia Ceccatto Ceará State University
    • Paula Soares Ceará State University
    • Gerly Brito
  • Biochemistry, McArdle Syndrome, Metabolism, Mitochondrial Metabolism, Myophosphorylase.
  • Carbohydrates are the main source of body energy and they can be stored in the organism in form of glycogen and degraded when there is a need for energy. However, McArdle Syndrome patients exhibit problems to degrade glycogen due to a deficiency in myophosphorylase enzyme, making these patients intolerant to high intensity exercises because a lack of ATP available in muscle cells. It has been found muscular weakness and subsarcolemmal accumulation of glycogen in muscle fibers and in neuronal cells in McArdle Syndrome patients. In its later-onset form, it is associated to muscular dysmorphia, myoglobinuria and rhabdomyolisis. Analyzing the biochemical aspects, it is possible to notice that these patients have a low rate of ATP production due to a reduction in the availability of glucose, reducing oxidative phosphorylation. However, the metabolic “second wind†effect allows the use of other energy sources. Excessively decreased exercise-induced lactate is also characteristic of patients with McArdle Syndrome. Electromyography studies describe alterations in nerve conduction and the necessity of recruiting more motor units to contract muscle in these patients. McArdle Syndrome produces several metabolic changes in patients due to absence of myophophorylase activity. The practice of aerobic exercise acts positively in these patients probably by increasing mitochondrial metabolism.

  • References

    1. [1] S.Tsujino, I.Nonaka, S.DiMauro,Glycogen storage myopathies,Neurologic clinics, 18 (2000) 125-150.

      [2] I.J.Wolfsdorf,I.A. Holm, D.A.Weinstein,Glycogen storage diseases: phenotypic, genetic, and biochemical characteristics, and therapy,Endocrinology and metabolism clinics of North America, 28 (1999) 801-823.

      [3] E. Gazzerro, A.L.Andreu, C.Bruno,Neuromuscular disorders of glycogen metabolism,Current neurology and neuroscience reports, 13 (2013) 1-12.

      [4] S.DiMauro, C.Lamperti,Muscleglycogenoses,Muscle& nerve, 24 (2001) 984-999.

      [5] J.Y.Chou, B.C.Mansfield,Mutations in the glucoseâ€6â€phosphataseâ€Î± (G6PC) gene that cause type Ia glycogen storage disease,Human mutation, 29 (2008) 921-930.

      [6] P.S.Kishnani, R.D.Steiner, D.Bali, et al.,Pompe disease diagnosis and management guideline,Genetics in Medicine, 8 (2006) 267-288.

      [7] S. Lucchiari, D.Santoro, S.Pagliarani, G.P.Comi,Clinical, biochemical and genetic features of glycogendebranching enzyme deficiencyActamyologica, 26 (2007) 72.

      [8] S.Li, C.M.Chen, L.J.Goldstein, et al., Glycogen storage disease type IV: novel mutations and molecular characterization of a heterogeneous disorder,Journal of inherited metabolic disease, 33 (2010) 83-90.

      [9] Y.SShin,Glycogen storage disease: clinical, biochemical, and molecular heterogeneity,Seminars in pediatric neurology, 13 (2006) 115-120.

      [10] N.J.Beauchamp, J.Taybert, M.P.Champion, et al.High frequency of missense mutations in glycogen storage disease type VI,Journal of inherited metabolic disease, 30 (2007) 722-734.

      [11] O.Musumeci, C.Bruno, T.Mongini, et al.Clinical features and new molecular findings in muscle phosphofructokinase deficiency (GSD type VII), Neuromuscular Disorders, 22 (2012) 325-330.

      [12] C.Lau, J.Hui, F.N.Hong, et al.Novel mutations in PHKA2 gene in glycogen storage disease type IX patients from Hong Kong, China,Molecular genetics and metabolism, 102 (2011) 222-225.

      [13] R.Santer, B.Steinmann, J.Schaub,Fanconi-Bickel syndrome-a congenital defect of facilitative glucose transport,Current molecular medicine, 2 (2002) 213-227.

      [14] A.Toscano, O. Musumeci,Tarui disease and distal glycogenoses: clinical and genetic update,ActaMyologica, 26 (2007) 105.

      [15] G.P.Comi, F.Fortunato, S.Lucchiari, et al.βâ€enolase deficiency, a new metabolic myopathy of distal glycolysis,Annals of neurology, 50, (2001) 202-207.

      [16] T.Stojkovic, J.Vissing, F.Petit, et al.Muscleglycogenosis due to phosphoglucomutase 1 deficiency,New England Journal of Medicine, 361(2009) 425-427.

      [17] M.Orho, N.O.Bosshard, N.R.Buist, et al.Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0,Journal of Clinical Investigation1998, 102(1998) 507.

      [18] C.M.Pearson, D.G.Rimer, W.F.Mommaerts,A metabolic myopathy due to absence of muscle phosphorylase,The American journal of medicine, 30(1961) 502-517.

      [19] A.Lucia,McArdle disease: what do neurologists need to know?,Nature Clinical Practice Neurology, 4 (2008) 568-577.

      [20] R.Quinlivan,McArdle disease: a clinical review.Journal of Neurology, Neurosurgery & Psychiatry, 81 (2010) 1182-1188.

      [21] R.Quinlivan, A.Martinuzzi, B.Schoser,Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V),Cochrane Database SystRevB (2010).

      [22] R.G.Haller, P.Wyrick, T.Taivassalo, J, et al.Aerobic conditioning: an effective therapy in McArdle's disease,Annals of neurology, 59 (2006) 922-928.

      [23] B.Saltin, P.D.Gollnick, Skeletal muscle adaptability: significance for metabolism and performance.Comprehensive Physiology, (2011)555–631.

      [24] A.Lucia, J.R.Ruiz, A. Santalla,et al.Genotypic and phenotypic features of McArdle disease: insights from the Spanish national registry,Journal of Neurology, Neurosurgery & Psychiatry, 83 (2012) 322-328.

      [25] B.McArdle,Myopathy due to a defect in muscle glycogen breakdown,Clinical Science, 10 (1951), 13-35.

      [26] M.A.Martín,Molecular heterogeneity of myophosphorylase deficiency (McArdle's disease): a genotypeâ€phenotype correlation study,Annals of neurology, 50 (2001) 574-581.

      [27] R.Aquaron, J.L.Bergé-Lefranc, J.F.Pelissier, et al,Molecular characterization of myophosphorylase deficiency (McArdle disease) in 34 patients from Southern France: identification of 10 new mutations. Absence of genotype–phenotype correlation,Neuromuscular Disorders, 17(2007) 235-241.

      [28] O.Rommel, R.A.Klay, G.Dekomien, J.T.Epplen, M.Vogerd, M.Hasenbring, Muscle pain in myophosphorylase deficiency (McArdle’s disease): the role of gender, genotype, and pain-related coping,Pain, 124 (2006) 295-304.

      [29] J.Zange, T.Grehl,C.Disselhorst-Klug,etal.Breakdown of adenine nucleotide pool in fatiguing skeletal muscle in McArdle's disease: A noninvasive 31Pâ€MRS and EMG study.Muscle& nerve, 27 (2003) 728-736.

      [30] F.Miteff, H.C.Potter, J.Allen, H.Teoh, R.Roxburgh, D.OHutchinson,Clinical and laboratory features of patients with myophosphorylase deficiency (McArdle disease).Journal of Clinical Neuroscience, 18(2011) 1055-1058.

      [31] A.Delibaş, K.Bek, F.S.Ezgü, G.Demircin, A.Oksal, A.Oner,Acute renal failure due to rhabdomyolysis in a child with McArdle disease,European journal of pediatrics, 167 (2008). 939-940.

      [32] P.J.Lorenzoni, M.C.Lange, C.S.Kay, R.H.Scola, L.C.Werneck,Motor nerve conduction study in McArdle disease: case report, Arquivos de neuro-psiquiatria, 63 (2005) 874-877

      [33] R.Costa, A.Costa, R.Taipa, R.Vizcaíno, T.Morgado,Mcardle disease presenting with rhabdomyolisis and acute kidney injury,Actamedicaportuguesa, 26 (2012) 463-466.

      [34] S.Moustafa, D.J.Patton, M.S.Connelly,Unforeseen Cardiac Involvement in McArdle's Disease,Heart, Lung and Circulation, 22(2013) 769-771.

      [35] D.P.Nicholls, N.P.Campbell, H.P.Stevenson, V.H.Patterson, Angina in McArdle's disease,Heart, 76(1996) 372-373.

      [36] J.Vissing, R.G.Haller,A diagnostic cycle test for McArdle's disease,Annals of neurology, 54 (2003)539-542.

      [37] N.Voduc, K.A.Webb, C.D'Arsigny, I.McBride, D.E.O'Donnell,McArdle's disease presenting as unexplained dyspnea in a young woman,Canadian respiratory journal, 11(2004) 163-167.

      [38] K.J. Felice, A.B.Schneebaum, H.R.Jones,McArdle's disease with late-onset symptoms: case report and review of the literature,Journal of Neurology, Neurosurgery & Psychiatry, 55 (1992) 407-408.

      [39] G.I.Wolfe, N.S.Baker, R.G.Haller, D.K.Burns, R.J.Barohn,McArdle's disease presenting with asymmetric, lateâ€onset arm weakness,Muscle& nerve, 23 (2000) 641-645.<641::AID-MUS25>3.0.CO;2-M.

      [40] A.A. Nadajâ€Pakleza, G.M.Vincitorio, P.Laforêt, et al. Permanent muscle weakness in McArdle disease,Muscle& nerve, 40(2009) 350-357.

      [41] J.C.Rubio, M.A.Martín, J.Bautista, et al.Myophosphorylase deficiency associated with a defect in complex I of the mitochondrial respiratory chain,Journal of the neurological sciences, 161 (1998) 110-113.

      [42] R.W.Byard, B.Laceu, D.N.Preston, Peripheral nerve and vasculature involvement in myophosphorylase deficiency (McArdle's disease), Pathology, 23 (1991) 62-65.

      [43] M. Scarpelli, G.Vattemi, M.Filosto, et al. McArdle disease and sporadic inclusion body myositis,Neuropathology and applied neurobiology, 35(2009) 442-445.

      [44] S.Tsujino, S.Shanske, J.E.Carroll,Double trouble: combined myophosphorylase and AMP deaminase deficiency in a child homozygous for nonsense mutations at both loci,Neuromuscular Disorders, 5 (1995) 263-266.

      [45] B.McArdle, D.Verel,Responses to ischaemic work in the human forearm,Clinical science (London), 15 (1956) 305-318.

      [46] H.M. Meinck, H.H.Goebel, K.W.Rumpf, H.Kaiser, P.Neumann, The forearm ischaemic work test--hazardous to McArdle patients?,Journal of Neurology, Neurosurgery & Psychiatry, 45 (1982) 1144-1146.

      [47] P.Kazemiâ€Esfarjani, R.Skomorowska, T.D. Jensen, R.G.Haller, J.Vissing, A nonischemic forearm exercise test for McArdle disease, Annals of neurology, 52(2002) 153-159.

      [48] S.F.Lewis, R.G.Haller,The pathophysiology of McArdle's disease: clues to regulation in exercise and fatigue,Journal of applied physiology, 61(1986) 391-401.

      [49] J. Vissing, R.G.Haller, The effect of oral sucrose on exercise tolerance in patients with McArdle's disease,New England Journal of Medicine, 349(2003) 2503-2509.

      [50] B.B.Pernow, R.J.Havel, D.B.Jennings,The second wind phenomenon in McArdle's syndrome.ActaMedicaScandinavica, 181(1967) 294-307.

      [51] S.T.Andersen, J.Vissing, Carbohydrate-and protein-rich diets in McArdle disease: effects on exercise capacity, Journal of Neurology, Neurosurgery & Psychiatry, 79(2008) 1359-1363.

      [52] R.Haller, W.B.Dempsey, H.Feit, J.D.Cook, J.PKnochel, Low muscle levels of pyridoxine in McArdle's syndrome, The American journal of medicine, 74(1983) 217-220.

      [53] J.Phoenix, P.Hopkins, C.Bartram, R.J.Beynon, R.C.Quinlivan, R.H.Edwards,Effect of vitamin B6 supplementation in McArdle's disease: a strategic case study,Neuromuscular Disorders, 8(1998) 210-212.

      [54] S.Sato, T.Ohi, I.Nishino, H.Sugie, Confirmation of the efficacy of vitamin B6 supplementation for McArdle disease by followâ€up muscle biopsy,Muscle& nerve, 45(2012) 436-440.

      [55] S.Lu, C.P.Lau, Y.Tung,Lactate and the effects of exercise on testosterone secretion: evidence for the involvement of a cAMP-mediated mechanism,Medicine and science in sports and exercise, 29(1997) 1048-1054.

      [56] R.J.Godfrey, G.P.Whyte, J.Buckley, R.Quinlivan,The role of lactate in the exercise-induced human growth hormone response: evidence from McArdle disease, British journal of sports medicine, 43(2009) 521-525.

      [57] S.T.Andersen, T.D.Jeppesen, T.Taivassalo, Effect of changes in fat availability on exercise capacity in McArdle disease,Archives of neurology, 66(2009) 762-766.

      [58] J.L.Maté-Munoz, M.Moran, M.Pérez, et al,Favorable responses to acute and chronic exercise in McArdle patients,Clinical Journal of Sport Medicine, 17(2007) 297-303.

      [59] A, Echaniz-Laguna, H.O. Akman, M. Mohr, et al.Musclephosphorylase b kinase deficiency revisited,Neuromuscular Disorders, 20(2010) 125-127.

      [60] M.Mancuso, D.Orsucci, D.Volterrani, S.Siciliano, Cognitive impairment and McArdle disease: Is there a link?, Neuromuscular Disorders, 21(2011) 356-358.

      [61] D.R.Rogers, D.T.MacIsaac,A comparison of EMG-based muscle fatigue assessments during dynamic contractions,Journal of Electromyography and Kinesiology, 23(2013) 1004-1011.

      [62] R.DHaller, T.Clausen, J.Vissing,Reduced levels of skeletal muscle Na+ K+-ATPase in McArdle disease,Neurology50(1998) 37-40.

      [63] T.Clausen, Na+-K+ pump regulation and skeletal muscle contractility.Physiological reviews, 83(2003) 1269-1324.

      [64] D.E.Rae, T.D.Noakes, A.F. San-Juan, et al,Excessive skeletal muscle recruitment during strenuous exercise in McArdle patients,European journal of applied physiology, 110(2010) 1047-1055.

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    Vieira, L., Soares, R., Felipe, S., Moura, F., Pacheco, C., Ceccatto, V., Soares, P., & Brito, G. (2015). Neuromuscular, cognitive and metabolic implications of McArdle Syndrome: a global overview. International Journal of Basic and Applied Sciences, 4(4), 422-428.