Laboratory Studies
Obtain a creatine kinase level in all cases of suspected GSD. Creatine kinase levels are elevated in more than 90% of patients with McArdle disease. Bruno and colleagues report a case of elevated creatine kinase on routine screening as the only sign of McArdle disease in a 13-year-old boy. [12]
Because hypoglycemia may be found in some types of GSD, fasting glucose testing is indicated. Hypoglycemia is of concern and may lead to hypoglycemic seizures.
Urine studies are indicated because myoglobinuria may occur in some patients with GSDs.
Hepatic failure occurs in some patients with GSDs. Liver function studies are indicated. In general, the liver contains little myophosphorylase.
Myoglobinuria is found in 50% of patients after exercise.
Biochemical assay is required for definitive diagnosis. Phosphorylase reaction is absent.
Other Tests
Ischemic forearm test
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The ischemic forearm test is an important tool for diagnosis of muscle disorders. The basic premise is an analysis of the normal chemical reactions and products of muscle activity. Obtain consent before the test.
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First instruct the patient to rest. Position a loosened blood pressure cuff on the arm, and place a venous line for blood samples in the antecubital vein.
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Obtain blood samples for the following tests: creatine kinase, ammonia, and lactate. Repeat in 5-10 minutes.
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Obtain a urine sample for myoglobin analysis.
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Immediately inflate the blood pressure cuff above systolic blood pressure and have the patient repetitively grasp an object, such as a dynamometer. Instruct the patient to grasp the object firmly, once or twice per second. Encourage the patient for 2-3 minutes, at which time the patient may no longer be able to participate. Immediately release and remove the blood pressure cuff.
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Obtain blood samples for creatine kinase, ammonia, and lactate immediately and at 5, 10, and 20 minutes.
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Collect a final urine sample for myoglobin analysis.
Interpretation of ischemic forearm test results
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With exercise, carbohydrate metabolic pathways yield lactate from pyruvate. Lack of lactate production during exercise is evidence of a pathway disturbance, and an enzyme deficiency is suggested. In such cases, muscle biopsy with biochemical assay is indicated.
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Healthy patients demonstrate an increase in lactate of at least 5-10 mg/dL and ammonia of at least 100 mcg/dL. Levels will return to baseline after the exercise is stopped.
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If neither level increases, the exercise was not strenuous enough and the test is not valid.
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Increased lactate at rest (before exercise) is evidence of mitochondrial myopathy.
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Failure of lactate to increase with ammonia is evidence of a GSD resulting in a block in carbohydrate metabolic pathways. Not all patients with GSDs have a positive ischemic test result.
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Failure of ammonia to increase with lactate is evidence of myoadenylate deaminase deficiency.
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If a patient has McArdle disease, the ischemic forearm test results are positive.
Electromyography
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In contrast to most GSDs, findings upon electromyography may be normal.
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Findings from electromyography of resting muscle are normal.
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Electrical activity is absent during contracture.
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Repetitive nerve stimulation at low frequency (2 Hz) does not demonstrate an abnormal response, although repetitive stimulation at high frequency (15 Hz) may produce a decrement with contracture formation.
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Single-fiber electromyography may reveal increased jitter.
Procedures
Muscle biopsy is necessary for assay of muscle enzyme activity.
Muscle biopsy findings may reveal fiber size variability, positive subsarcolemmal blebs with periodic acid-Schiff stain, and intermyofibril vacuoles. Felice and colleagues reported selective atrophy of type 1 muscle fibers. [13]
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Metabolic pathways of carbohydrates.
