Glycogen StorageDiseases
Glycogen storage diseases are so namedbecause a hallmark of the diseases is impaired glycogen storage dueto a deficiency of one of the enzymes involved in either glycogensynthesis or glycogen degradation. Several kinds of glycogenstorage diseases have been identified so far. Each type ischaracterized by the lack of a specific enzyme. An understanding ofglycogen metabolism is essential in the proper treatment of thisdisease, and identification of the deficient enzyme is requiredbefore a treatment protocol can be designed.
Your patient is a fifteen-year-oldCaucasian male named Joe K. Joe canât perform any kind of strenuousexercise. During his physical education classes, Joe could not keepup with his classmates and often suffered painful muscle cramps ifhe did attempt to exercise. He appeared to be normal if at rest orperforming light to moderate exercise. A physical examinationreveals that his liver appears to be normal in size, but hismuscles are flabby and poorly developed. A fasting glucose testshowed that Joe was not hypo- or hyperglycemic. A number ofbiochemical tests were carried out to identify the type of glycogenstorage disease in this patient.
Questions
1. You decide to try Joeâs response to glucagon. This testconsists of injecting a high dose of glucagon intravenously andthen drawing samples of blood periodically and measuring theglucose content of the samples. After the glucagon injection, Joeâsblood sugar rises dramatically. Is this the response you wouldexpect in a normal person? Explain.
2. Liver and musclebiopsies are taken from Joe and analyzed.
The biopsies revealed that glycogencontent in the liver is normal, but muscle glycogen content iselevated. The biochemical structure of glycogen in both tissuesappears to be normal. Suggest some possible explanations for theseobservations.
3. Next, you do another testwhere you have Joe perform ischemic exercise for as long as he isable to do so.
The ischemic exercise consists of thepatient squeezing a hand dynamometer at maximal strength for aspecific period of time, usually 1 minute, with an occlusionpressure cuff, which is placed on the upper arm and set at 250mmHg, blocking blood flow to the exercising arm. Blood is withdrawnfrom the patient every few minutes or so during the exerciseperiod.
a. Joeâs blood samples are tested forlactate and compared with a control sample of a patient who doesnot suffer from a glycogen storage disease. The results are shownin the plot to the right. Why does lactate concentration increasein the normal patient?
b. Why is there no correspondingincrease in Joeâs lactate concentration?
4. Urine tests after Joe has completedhis exercise reveal the presence of myoglobin in his urine.Myoglobin isnât normally found in the urine, but in muscle cells.Why does Joe suffer from myoglobinuria following ischemicexercise?
5. Joeâs enzyme deficiency does notcause him to suffer from either hypo- or hyperglycemia. Explainwhy.
6. As a treatment, you tell Joe thatthe best thing he can do is to avoid strenuous exercise. If he doeswish to exercise, you advise him to consume sports drinkscontaining glucose or fructose frequently while exercising. Whywould this help alleviate Joeâs suffering during exercise?
Glycogen StorageDiseases
Glycogen storage diseases are so namedbecause a hallmark of the diseases is impaired glycogen storage dueto a deficiency of one of the enzymes involved in either glycogensynthesis or glycogen degradation. Several kinds of glycogenstorage diseases have been identified so far. Each type ischaracterized by the lack of a specific enzyme. An understanding ofglycogen metabolism is essential in the proper treatment of thisdisease, and identification of the deficient enzyme is requiredbefore a treatment protocol can be designed.
Your patient is a fifteen-year-oldCaucasian male named Joe K. Joe canât perform any kind of strenuousexercise. During his physical education classes, Joe could not keepup with his classmates and often suffered painful muscle cramps ifhe did attempt to exercise. He appeared to be normal if at rest orperforming light to moderate exercise. A physical examinationreveals that his liver appears to be normal in size, but hismuscles are flabby and poorly developed. A fasting glucose testshowed that Joe was not hypo- or hyperglycemic. A number ofbiochemical tests were carried out to identify the type of glycogenstorage disease in this patient.
Questions
1. You decide to try Joeâs response to glucagon. This testconsists of injecting a high dose of glucagon intravenously andthen drawing samples of blood periodically and measuring theglucose content of the samples. After the glucagon injection, Joeâsblood sugar rises dramatically. Is this the response you wouldexpect in a normal person? Explain.
2. Liver and musclebiopsies are taken from Joe and analyzed.
The biopsies revealed that glycogencontent in the liver is normal, but muscle glycogen content iselevated. The biochemical structure of glycogen in both tissuesappears to be normal. Suggest some possible explanations for theseobservations.
3. Next, you do another testwhere you have Joe perform ischemic exercise for as long as he isable to do so.
The ischemic exercise consists of thepatient squeezing a hand dynamometer at maximal strength for aspecific period of time, usually 1 minute, with an occlusionpressure cuff, which is placed on the upper arm and set at 250mmHg, blocking blood flow to the exercising arm. Blood is withdrawnfrom the patient every few minutes or so during the exerciseperiod.
a. Joeâs blood samples are tested forlactate and compared with a control sample of a patient who doesnot suffer from a glycogen storage disease. The results are shownin the plot to the right. Why does lactate concentration increasein the normal patient?
b. Why is there no correspondingincrease in Joeâs lactate concentration?
4. Urine tests after Joe has completedhis exercise reveal the presence of myoglobin in his urine.Myoglobin isnât normally found in the urine, but in muscle cells.Why does Joe suffer from myoglobinuria following ischemicexercise?
5. Joeâs enzyme deficiency does notcause him to suffer from either hypo- or hyperglycemia. Explainwhy.
6. As a treatment, you tell Joe thatthe best thing he can do is to avoid strenuous exercise. If he doeswish to exercise, you advise him to consume sports drinkscontaining glucose or fructose frequently while exercising. Whywould this help alleviate Joeâs suffering during exercise?
