Type VI Glycogen Storage Disease Workup

Updated: Aug 12, 2021
  • Author: Ranjodh Singh Gill, MD, FACP, CCD; Chief Editor: George T Griffing, MD  more...
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Laboratory Studies

Obtain a creatine kinase level in all cases of suspected glycogen storage disease (GSD).

Because hypoglycemia may be found in some types of GSD, fasting glucose testing is indicated. In GSD VI disease, hypoglycemia is a primary concern.

Urine studies are indicated because myoglobinuria may occur in some patients with GSDs.

Liver function studies are indicated and may reveal evidence of hepatic injury.

Biochemical assay of enzyme activity is necessary for definitive diagnosis. 

Molecular testing of the gene responsible for GSD VI (PYGL) is done first if the patient is female.

Testing of the gene responsible for GSD IX (phosphorylase kinase, liver, alpha-2 subunit [PHKA2]) is done first if the patient is male.

Liver biopsy may be indicated in selective cases.

Manzia et al reported the first documented case of GSD associated with a rapidly growing hepatocellular adenoma as determined by histologic findings. [13]


Imaging Studies

Liver ultrasound scanning for diagnosis and surveillance should be performed.

Bone density testing should be assessed once the patient has stopped growing. [14]


Other Tests

Ischemic forearm test

In the case of GSD VI disease, which is not associated with significant muscle involvement, the forearm ischemic test is most useful to help rule out other GSDs, most specifically Cori disease, McArdle disease, and Tarui disease. Test findings are expected to be negative in patients with Hers disease.

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.

Positive ischemic forearm test results may occur in patients with Cori disease, McArdle disease, and Tarui disease.

In patients with GSD VI disease, ischemic test results are negative.