Clinical History
A 15-year-old adolescent has been bothered by painful muscle cramps during physical education classes at school. This has been occurring over the past couple of months. His coach just tells him, "Work it off with a few more laps around the track." The boy believes that there is a more serious problem, because his urine is darker following these episodes. The boy's family physician refers him to a neurologist. The neurologist determines that electromyography is normal at rest.
The image demonstrates the glycogen deposited in muscle, seen as the red deposits with PAS stain.
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- Which of the following laboratory test findings in the patient's blood is most likely to be present?
- A. Increased D-dimer
- B. No rise in lactate after exercise
- C. Positive antinuclear antibody test
- D. Increased troponin I
- E. Normal serum creatine kinase
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Answer: B The findings suggest myophosphorylase deficiency, or type V glycogen storage disease. The creatine kinase is increased with strenuous exercise, but the blood lactate does not rise because the glycolytic pathway of muscle metabolism is not functional.
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- Which of the following histopathologic findings is most likely to be seen in a skeletal muscle biopsy?
- A. Lack of staining for dystrophin
- B. Grouped atrophy
- C. Diminished size and number of type II fibers
- D. PAS positive deposits
- E. Infiltration by T cells
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Answer: D There is a buildup of glycogen deposits with myophosphorylase deficiency, an autosomal recessive condition.
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- Which of the following organs is most likely to be affected by this condition?
- A. Liver
- B. Brain
- C. Kidney
- D. Heart
- E. Adrenal
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Answer: C The dark urine following exercise suggests something is being excreted. That something is myoglobin. If the myoglobinuria is severe, acute tubular necrosis and renal failure can occur.
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- Which of the following long-term outcomes of this patient's disease is most likely to occur?
- A. Inability to perform competitive sports
- B. Neurologic deterioration
- C. Hepatic cirrhosis
- D. Congestive heart failure
- E. Chronic renal failure
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Answer: A The symptoms of McArdle's disease do not occur when strenuous exercise is avoided. There are no long term organ failures with this disease.
Explain the biochemistry of this disease.
Glycogen is stored in skeletal muscle and can be metabolized to glucose to provide a substrate for energy production. The glycolytic pathway can provide a quick but inefficient source of ATP under conditions of strenous exertion. Absence of the myophosphorylase enzyme means that glycogen cannot be cleaved at 1,4-glycosidic chains to produce glucose. Ordinarily, glucose is then metabolized via the hexokinase enzyme to glucose-6-phosphate. Glucose-6-phosphate then is metabolized to glyceraldehyde-3-phosphate and then to 3-phosphoglycerate with production of ATP. The phosphoglycerate becomes phosphoenolpyruvate which is metabolized to pyruvate with ATP production. THe net yield is 2 ATP per glucose, far less than from the oxidative citric acid (Krebs) cycle (with a theoretical yield of 38 ATP per glucose, but more like 30 after subtracting for mitochondrial needs), but more readily available. Glycolysis also increases the amount of NADH which favors reduction of pyruvate to lactate. In order to restore balance, oxidative metabolism is required, so during periods of anaerobic glycolysis, an "oxygen debt" develops. Tissues that have less oxygenated blood flow (ischemia) resort to anaerobic glycolysis, and the blood lactate rises.
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