Type IV Glycogen Storage Disease Workup

Updated: Apr 25, 2014
  • Author: Wayne E Anderson, DO, FAHS, FAAN; Chief Editor: George T Griffing, MD  more...
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Workup

Laboratory Studies

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  • Obtain a creatine kinase level in all cases of suspected glycogen storage diseases (GSDs).
  • Because hypoglycemia may be found in some types of GSD, fasting glucose testing is indicated.
  • Urine studies are indicated because myoglobinuria may occur in some GSDs.
  • Hepatic failure occurs in some GSDs. Liver function studies are indicated and may reveal evidence of hepatic injury.
  • Biochemical assay of enzyme activity is necessary for definitive diagnosis. Glycogen structure is altered, with fewer branching points and longer peripheral chains. This abnormal glycogen structure is absent in other GSDs.
  • Shen and colleagues demonstrated that DNA mutation analysis by polymerase chain reaction is effective for prenatal diagnosis. [8]
  • Akman and colleagues demonstrated that prenatal diagnosis of GSD IV by DNA analysis is accurate in the genetically confirmed cases. [9]
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Imaging Studies

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  • Imaging may reveal hepatosplenomegaly.
  • Imaging also may reveal cardiomyopathy and heart failure.
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Other Tests

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  • Ischemic forearm test
    • The ischemic forearm test is an important tool for the 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 from 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 a positive ischemic test.
    • Failure of ammonia to increase with lactate is evidence of myoadenylate deaminase deficiency.
    • A positive ischemic forearm test may occur in Cori disease, McArdle disease, and Tarui disease.
  • Electromyelography
    • Electromyelography patterns are diverse and vary from patient to patient.
    • Myopathic polyphasic responses are found, but amplitude and duration may be either decreased, as expected, or increased.
    • Spontaneous abnormal activity (fibrillation potential and positive sharp waves) may be found.
    • Myotonic discharges occur in some cases.
  • Electrocardiogram: A prolonged QT interval may be present.
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Procedures

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  • Liver biopsy may be needed to determine the cause of progressive liver dysfunction. Histologic findings are characteristic in the liver, with diffuse interstitial fibrosis, wide fibrous septa, and enlarged hepatocytes with periodic acid-Schiff positive inclusions. Electron microscopy shows alpha and beta glycogen particles.
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Histologic Findings

Diffuse deposition of amylopectinlike materials in the heart, liver, muscle, spinal cord, and peripheral nerves may be present.

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