Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 3197  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (1,622 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

  In this Article
 »  Abstract
 » Introduction
 » Case Reports
 »  Materials and Me...
 » Results
 » Discussion
 »  References
 »  Article Figures

 Article Access Statistics
    PDF Downloaded90    
    Comments [Add]    
    Cited by others 1    

Recommend this journal


Table of Contents    
Year : 2011  |  Volume : 59  |  Issue : 6  |  Page : 884-886

Glycogen storage disease type V (Mc Ardle's disease): A report on three cases

1 Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India
2 Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India
3 Department of Neurology, Madras Medical College, Chennai, India

Date of Submission18-May-2011
Date of Decision11-Jun-2011
Date of Acceptance16-Jul-2011
Date of Web Publication2-Jan-2012

Correspondence Address:
N Gayathri
Department of Neuropathology, NIMHANS, Bangalore - 560 029
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.91370

Rights and Permissions

 » Abstract 

McArdle's disease (myophosphorylase deficiency), an uncommon autosomal recessive metabolic disorder, is characterized clinically by exercise intolerance beginning in childhood, myalgia, cramps, exercise-induced rhabdomyolysis, "second wind" phenomenon, elevated Creatine Kinase (CK) levels at rest, and previous episodes of raised CK levels following exercise. Several mutations in the PYGM gene and geographic variations have been described. We report three biopsy confirmed cases of McArdle's disease.

Keywords: Exercise intolerance, McArdle′s disease, myophosphorylase

How to cite this article:
Krishnamoorthy N, Santosh V, Yasha T C, Mahadevan A, Shankar S K, Jethwani D, Taly A B, Bhanu K, Gayathri N. Glycogen storage disease type V (Mc Ardle's disease): A report on three cases. Neurol India 2011;59:884-6

How to cite this URL:
Krishnamoorthy N, Santosh V, Yasha T C, Mahadevan A, Shankar S K, Jethwani D, Taly A B, Bhanu K, Gayathri N. Glycogen storage disease type V (Mc Ardle's disease): A report on three cases. Neurol India [serial online] 2011 [cited 2021 Aug 2];59:884-6. Available from:

 » Introduction Top

McArdle's disease (myophosphorylase deficiency), an uncommon autosomal recessive metabolic disorder is characterized clinically by exercise intolerance, beginning in childhood, myalgia, cramps, exercise-induced rhabdomyolysis, second wind phenomenon, Elevated Creatine Kinase (CK) levels at rest, and previous episodes of raised CK levels following exercise. Mutations in the PYGM gene encoding myophosphorylase on chromosome 11 and genetic variants of several genes determine the severity of phenotype and geographic variations. Genotype-phenotype correlations have been attempted with an insertion-deletion in Angiotensin Converting Enzyme (ACE) gene favoring less severe phenotype, while coexistence of mutation in muscle Adenylate Deaminase 1 (AMPD1) being associated with severe phenotype. Existence of geographic variation is suggested by finding of mutation in exon 1 (p.R50X) in Caucasians, p.F710 deletion in Japanese, and p.W798R in Spanish population. [1] In view of genetic heterogeneity, enzyme stain for myophosphorylase on muscle biopsy still remains the gold standard for diagnosis. To the best of our knowledge, there are no reports of McArdle's disease from India. Here, we report three biopsy-confirmed cases of McArdle's disease.

 » Case Reports Top

Case 1

A 21-year-old male, born of non-consanguineous marriage, was apparently healthy till 9 years of age, when he started having recurrent episodes of muscle pain, precipitated by exertion and seizures. Seizures were of generalized tonic clonic, absence, and photosensitivity type. He had an ill-defined aura (upper abdominal discomfort and anxiety) before the seizures. He was hospitalized for these symptoms on two occasions and underwent dialysis for acute renal failure due to myoglobinuria. During present admission, he complained of episodes of pain and cramps while walking uphill, which improved after rest, allowing him to walk further (second wind phenomenon). On examination, the patient had pain on sustained grip. Muscle tone, power, and reflexes were normal. Serum CK on several occasions was elevated (3,000 to 3.8 lakh IU/L) (Normal, 30-194 IU/L). During present evaluation, CK was 2,999 IU/L. All other hematological and biochemical parameters (LFT, RFT, lactate) were normal. Electromyography (EMG) showed a myopathic pattern.

Case 2

A 16-year-old male, born of non-consanguineous marriage was apparently healthy till 14 years of age, when he started having recurrent episodes of groin pain associated with vomiting following rigorous exercise (relay race and swimming), leading to renal failure on two occasions. Serum CK was 864 IU/L. A similar history was noted in his father 25 years back, for which he was not evaluated. General and systemic examination of the patient was normal. Resting serum CK was 172 IU/L, EMG was not performed.

Case 3

A 37-year-old male, admitted with 6 years duration of spasmodic contracture of right hand and fingers flexors after exertion, followed by symmetrical contracture of the right arm. Three years later, the patient developed spasmodic contracture of right toes, calf, and thigh after exertion. On examination, muscle cramps were present during forceful contraction of forearm, calf, and hand muscles. Resting serum CK was 32 IU/L. EMG was not performed.

 » Materials and Methods Top

All patients were subjected to muscle biopsy for diagnosis (biceps, case 1 and 2; quadriceps, case 3). Biopsies were processed for light and electron microscopic examination. Frozen sections were stained for succinic dehydrogenase, nicotinamide adenine dinucleotide tetrazolium reductase, adenosine triphosphatase pH 9.4, 4.6, acid phosphatase, myophosphorylase, Hematoxylin and Eosin (H and E), Periodic Acid Schiff (PAS), PAS-diastase, Oil red O and Modified Gomori's Trichrome. Tiny fragments of muscle fixed in 3% buffered glutaraldehyde was post fixed in osmium tetroxide and embedded in araldite. Ultra-thin sections contrasted with uranyl acetate and lead citrate were scanned under JEOL 100CX electron microscope.

 » Results Top

Histologically, muscle biopsies revealed normal histology [Figure 1]a in all cases, except for a scattered fiber undergoing myophagocytosis [Figure 1]b. No vacuoles were discernible in any of the cases. Enzyme Stain for phosphorylase [Figure 2]a was found to be deficient [Figure 2]b in all three cases, while the remaining enzyme stains were unremarkable. Ultrastructurally, aggregation of glycogen granules was noted at I band [Figure 3]a subsarcolemmal and intermyofibrillar regions [Figure 3]b in all three cases. Occasionally, myelinic figure and lipofuscin material were also evident.
Figure 1: Transversely cut skeletal muscle tissue showing normal polygon-shaped fibers, (a) and an occasional myophagocytosis (↑) (b); H and E, ×200

Click here to view
Figure 2: Enzyme stain for myophosphorylase shows normal staining pattern, (a) complete absence (b); ×200

Click here to view
Figure 3: Electron micrographs showing (a) aggregation of glycogen granules at I band, (b) subsarcolemmal region; ×20,000

Click here to view

 » Discussion Top

Glycogen storage disease due to myophosphorylase deficiency first described by McArdle is characterized by gross failure of the breakdown of glycogen to lactic acid, [2] with an incidence of 1/100,000. Subsequently, there have been several reviews on clinical and genetic aspects. [3],[4]

We report three cases of McArdle's disease confirmed by enzyme histochemical staining for myophosphorylase. All three patients in the present study were males with early childhood onset (<12 years) in cases 1 and 2 and adult onset (31 years) in case 3. According to previous reports, the onset of McArdle's disease varies from early/late childhood to adulthood and rare cases of late-onset forms (>60 years) with female preponderance has also been reported. Clinically, exercise intolerance, an important diagnostic clue, was noted in all cases. The disease severity as per four-class grading system proposed by Martunizzi et al., [5] was scored as grade 1 (case 3) and grade 2 (cases 1 and 2). Contractures and seizures, though rare, have been reported. [6],[7] The second wind phenomenon, which is a classical symptom of McArdle's disease, was noted in two of our patients. This is attributed to the fact that first few minutes of exercise act as warm up, making more glucose available to the muscle fibers. The upstream blockade in glycogenolysis, which is seen in McArdle's disease is partially bypassed, leading to attenuation of fatigue. [8],[9] Although McArdle's disease is not a life-threatening condition, severe stress on the muscle leads to acute renal failure as noted in two of our patients. Elevated CK levels at rest and previous episodes of hyper-CK-emia following stress are useful indicators as noted in our cases. There were no specific findings on light microscopy. The subsarcolemmal accumulation of glycogen could be appreciated only on electron microscopy. These are probably milder cases of McArdle's disease, where PAS stain fails to show any focal accumulation of glycogen. [10] Hence, in an appropriate clinical setting, absence of myophosphorylase staining on muscle biopsy, as seen in all our cases, clinches the diagnosis. Myophosphorylase activity can be reduced by other factors such as malnutrition, severely denervated muscle, and in biopsy specimens held for several hours before freezing. [11] These factors were excluded in all three cases. Till date, there is no definitive cure or therapeutic modalities for McArdle's disease. Diet rich in complex carbohydrates and lifestyle modifications (monitoring regular aerobic exercise of low to moderate intensity and ingesting simple carbohydrates before strenuous exercise) can benefit patients. [12]

In the absence of genetic testing, fresh muscle biopsy with specific enzyme histochemistry to demonstrate myophosphorylase deficiency is useful in establishing the diagnosis of this rare condition. Simple measures of lifestyle modification and dietary changes are effective in preventing morbidity and renal failure.

 » References Top

1.Lucia A, Nogales-Gadea G, Pérez M, Martín MA, Antoni L, Andreu AL, et al. Mc Ardles disease: What do neurologists need to know? Nat Clin Pract Neurol 2008;4:568-77.  Back to cited text no. 1
2.Mc Ardle B. Myopathy due to a defect in muscle glycogen breakdown. Clin Sci 1951;10:13-33.  Back to cited text no. 2
3.Di Mauro, Andreu AL, Bruno C, Hadjigeorgiou GM. Myophosphorylase deficiency (glycogenosis type V; Mc Ardle disease). Curr Mol Med 2002;2:189-96.  Back to cited text no. 3
4.Martinuzzi A, Schievano G, Nascimbeni A, Fannin M. The unsolved mystery of reappearing enzyme. Am J Pathol 1999;154:1893-7.  Back to cited text no. 4
5.Martinuzzi A, Sartori E, Fanin M, Valente L, Angelini C, Siciliano G, et al. Phenotype modulators in myophosphorylase deficiency. Ann Neurol 2003;53:497-502.  Back to cited text no. 5
6.Lewis SF, Haller RG. The pathophysiology of Mc Ardle's disease: Clues to regulation in exercise and fatigue. J Appl Physiol 1986;61:391-401.  Back to cited text no. 6
7.Salmon S, Turner C. Mc Ardle's disease presenting as convulsions and rhabdomyolysis. Acta Myol 2007;26:35-41.  Back to cited text no. 7
8.Zange J, Grehi T, Disselhorst-Klug C, Rau G, Muller K, Rolf S. Breakdown of adenine nucleotide pool in fatiguing skeletal muscle in Mc Ardle's disease-a noninvasive 31P-MRS and EMG study. Muscle Nerve 2003;27:728-36.  Back to cited text no. 8
9.Pearson CM, Rimer DG, Mommaerts WF. A metabolic myopathy due to absence of muscle phosphorylase. Am J Med 1961;30:502-17.  Back to cited text no. 9
10.DiMauro S, Hays A, Sujino S. Metabolic disorders affecting muscle. In: Engel A, Franzini-Armstrong C, editors. Myology Basic and Clinical. 3 rd ed. New York: McGraw- Hill; 2004;2:1539.  Back to cited text no. 10
11.Griggs RC, Mendell J, Miller R. In: Evaluation and treatment of myopathies: Philadelphia: F.A Davis Company; 1995. p. 257.  Back to cited text no. 11
12.Maté-Muñoz JL, Moran M, Pérez M, Chamorro-Viña C, Gómez-Gallego F, Santiago C, et al. Favourable responses to acute and chronic exercise in Mc Ardles patients. Clin J Sport Med 2007;17:297-303.  Back to cited text no. 12


  [Figure 1], [Figure 2], [Figure 3]

This article has been cited by
1 McArdle Disease: A Unique Study Model in Sports Medicine
Alfredo Santalla,Gisela Nogales-Gadea,Niels Ørtenblad,Astrid Brull,Noemi de Luna,Tomàs Pinós,Alejandro Lucia
Sports Medicine. 2014; 44(11): 1531
[Pubmed] | [DOI]


Print this article  Email this article
Online since 20th March '04
Published by Wolters Kluwer - Medknow