Laboratory Studies

Obtain a creatine kinase level in all cases of suspected glycogen storage disease (GSD). In patients with Tarui disease, creatine kinase levels are elevated.

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. In patients with Tarui disease, myoglobinuria may be present after exercise.

Evidence of mild hemolytic anemia can be found, including increased bilirubin and reticulocyte count.

Hepatic failure occurs in some patients with GSDs. Liver function studies are indicated.

Biochemical assay reveals normal phosphorylase activity. Muscle PFK is absent on histochemistry assay, whereas erythrocyte PFK activity is reduced to about 50% of normal PFK.

Some specific features that may help differentiate Tarui disease from McArdle disease include the following:

Compensated hemolytic anemia in GSD type VII
Hyperuricemia that is worsened by exercise in Tarui disease

Ischemic forearm test

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.

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.

Obtain blood samples for the following tests: creatine kinase, ammonia, and lactate. Repeat in 5-10 minutes. Obtain a urine sample for myoglobin analysis.

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.

Obtain blood samples for creatine kinase, ammonia, and lactate immediately and at 5, 10, and 20 minutes. Collect a final urine sample for myoglobin analysis.

Interpretation of ischemic forearm test results

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.

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. If neither level increases, the exercise was not strenuous enough and the test is not valid.

Increased lactate at rest (before exercise) is evidence of mitochondrial myopathy. 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 positive ischemic test results. Failure of ammonia to increase with lactate is evidence of myoadenylate deaminase deficiency. In patients with Tarui disease, ischemic forearm test results are positive.

Electromyography

Findings on electromyography testing in patients with phosphofructokinase deficiency may be normal. Findings from electromyography of resting muscle are normal. Electrical activity is absent during contracture.

Repetitive nerve stimulation at low frequency (2 Hz) does not demonstrate an abnormal response, while repetitive stimulation at high frequency (15 Hz) may produce a decrement with contracture formation.

Single-fiber electromyography may reveal increased jitter.

Histologic Findings

Muscle biopsy is necessary for definitive diagnosis.

Findings from muscle biopsy may reveal subsarcolemmal vacuoles. Red blood cell examination indicates moderate hemolytic anemia. Phosphorus-31 magnetic resonance spectroscopy may help establish diagnosis. Abnormal polysaccharide, which is resistant to diastase digestion, is present in muscle fibers but is not seen in patients with McArdle disease (GSD type V).

Treatment & Management

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