Final Diagnosis -- McArdle's Disease



Muscle phosphorylase enzyme histochemistry in a control muscle shows the normal checkerboard staining pattern. Phosphorylase staining was absent in the patient's muscle.

Additional biochemical activity assays (Athena Diagnostics, Worcester, MA) are presented in the table below

Phosphorylase A
Myoadenylate deaminase

*Normal values are 50% of the mean. Abnormal values are in "bold".




The exercise-induced myalgias, burning pain, and elevated CK suggested a metabolic myopathy. (1,2) Any disturbance in the biochemical pathways that support ATP levels in the muscle will lead to exercise intolerance which leads to true fatigue - an unpleasant sensation that occurs when the muscle will no longer perform properly. The onset of symptoms soon after exercise made a defect in glycolysis more likely than a defect in lipid metabolism. A mitochondrial myopathy was also a consideration. The positive family history in two generations raised the possibility of an autosomal dominant disorder, but the other possibly affected members were not available for examination. Most inherited metabolic myopathies are of autosomal recessive inheritance except for phosphoglycerate kinase deficiency (X-linked), phosphorylase b kinase deficiency (X-linked as well as autosomal recessive), and mitochondrial myopathies (maternal or autosomal inheritance). For unclear reasons, many of the autosomal recessive glycolytic disorders and carnitine palmityltransferase deficiency affect males more than females.

In our patient, the EMG abnormalities were most striking in the paraspinal muscles. Preferential paraspinal abnormalities are common in inflammatory myopathies and in acid maltase deficiency (a lysosomal glycogen storage disease that does not cause myalgias), but they are not well-described in other metabolic myopathies. In a previous publication, we presented this patient within a small series and discussed the importance of the paraspinal EMG and histopathology findings. (reproduced with permission from reference 3)

The histopathology of the paraspinal muscle showed the classical changes of phosphorylase deficiency (McArdle's Disease). Phosphorylase deficiency is an autosomal recessive disorder. Despite the biochemical homogeneity, various point mutations on chromosome 11 have been identified denoting genetic heterogeneity. (4) There are two forms of the enzyme -- a, the active tetramer; and b, the inactive dimer. The conversion of b to a is facilitated by phosphorylase kinase (which itself is activated by a protein kinase under the control of cyclic AMP.

Patients with phosphorylase deficiency usually present with childhood to adult onset of muscle pain or contracture following brief, strenuous exercise. They may develop rhabdomyolysis with myoglobinuria. (1, 5) With a reduction in exercise and slower resumption, they may get a "second wind" as lipid metabolism kicks in. Our patient did not note such a phenomenon. As in our patient, those affected may develop proximal weakness after successive attacks. Our patient also had myalgias at rest for unclear reasons.

The laboratory features of phosphorylase deficiency usually include a highly elevated CK during attacks and a normal or mildly elevated CK at baseline. Ischemic lactate testing reveals a failure to raise serum lactate (the end product of glycolysis); the ammonia rise is normal. The EMG may be normal or reveal characterisitic myopathic changes with fibrillation potentials (especially during attacks). We also observed the presence of prominent paraspinal muscle spontaneous activity on EMG without such findings in the limb muscles. The muscle pathology which we described is characteristic of this disorder, but the findings in the paraspinal muscles were again more dramatic than in the limb muscle illustrating that there may be histopathologic variability from muscle to muscle in this glycogen strorage disease just as there is in acid maltase deficiency. (6)

The treatment of McArdle's Disease is limited to hydration with alkaline diuresis during acute attacks. Specific therapies are not yet available.


  1. Hilton-Jones D, Squier MV, Taylor D, Matthews PM (eds). Metabolic Myopathies. London, WB Saunders Co. Ltd., 1995. pp 1-21.
  2. Griggs RC, Mendell JR, Miller RG (eds): Evaluation and treatment of myopathies. Philadelphia, FA Davis Co., 1995.
  3. Petrella JT, Giuliani MJ, Lacomis D.Vacuolar myopathies in adults with myalgias: Value of paraspinal muscle investigation. Muscle Nerve 1997;20:1321- 1323. copyright John Wiley & Sons, Inc.
  4. Tsujono S, Shanske S, DiMauro S. Molecular genetic heterogeneity in myophosphorylase deficiency (McArdle's Disease). N Engl J Med 329:241-245, 1993
  5. DiMauro S, Tsujino S: Nonlysosomal glycogenoses, in Engel AG, Franzini- Armstrong C (eds): Myology, second ed. New York, McGraw Hill, 1994. pp 1554-1576.
  6. van der Walt JD, Swash M, Leake J, Cox EL. The pattern of involvement of adult- onset acid maltase deficiency at autopsy. Muscle Nerve 10:272-281, 1987

Acknowledgment: Matt Morrow, M.D. kindly referred the patient to us. This patient was previously reported in less detail as patient 1 in Vacuolar Myopathies in Adults with Myalgias: Value of Paraspinal Muscle Investigation, J. Terry Petrella, Michael J. Giuliani and David Lacomis: Muscle and Nerve 20:1321-1323, 1997. That report included black and white figures of the H&E and PAS stains, copyright ( 1997 John Wiley & Sons, Inc. These figures are reproduced with permission of John Wiley & Sons, Inc.

Contributed by David Lacomis, MD* † and Michael J. Giuliani, MD*


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