Question

A patient is a fifteen-year-old male named Alex. Alex’s mother has brought him to see you because she is concerned about his inability to perform any kind of strenuous exercise. During his physical education classes, alex could not keep up with his classmates and often suffered painful muscle cramps if he attempted to exercise. He appeared to be normal if at rest or performing light to moderate exercise. A fasting glucose test showed that Kyle was not hypoglycemic or hyperglycemic. You suspect alex is suffering from a glycogen storage disease.

1. You decide to try Alex’s response to glucagon. This test consists of injecting a high dose of glucagon intravenously and then drawing samples of blood periodically and measuring the glucose content of the samples. Explain the reason behind why prescribing this test.

2. After the glucagon injection, alex’s blood sugar rises in the range expected of a normal person. An analysis of liver and muscle biopsies taken from alex reveals that while the glycogen content in his liver is normal, the muscle glycogen content is elevated. However, the biochemical structure of glycogen in both tissues appears to be normal. Based on this information, can you start to narrow down the enzyme deficiency that alex may be suffering from? Explain your answer.

3. Next, you do another test where you have alex perform ischemic exercise for as long as he is able to do so. Blood is withdrawn every few minutes or so during the exercise period. alex’s blood samples are tested for lactate and compared with a control sample of a patient who does not suffer from a glycogen storage disease. The results indicate that the lactate concentration increases in the normal patient as expected, but there is no increase in alex’s lactate concentration. How does this help you confirm your diagnosis further? Explain your answer.

4. Considering your diagnosis, do you think this will also affect alex’s ability to secrete insulin after eating a meal and/or to mount an appropriate biochemical response to insulin? Explain your answer.

Answer 1

1.Glycogen storage disease type 5 is a disorder in which the main symptom is exercise intolerance.This disorder is mainly caused because of the lack of muscle glycogen phosphorylase enzyme hence this test is prescribed since glucagon helps in breaking glycogen to glucose.

2. This test confirms that the boy is suffering from deficiency of muscle glycogen phosphorylase enzyme. This enzyme initiates the breakdown of glycogen. This the reason why there is elevated amount of glycogen in the muscle.

3. Persons with deficiency of glycogen phosphorylase enzyme does not produce lactate during exercise. This is because there is no breakdown of glycogen molecule which automatically preserves the oxidation of glucose.

4. Insulin action is reduced in patients with McArdle's disease.