A 15-year-old boy is brought to the clinic due to poor exercise endurance. He recently began weight lifting with friends but has had difficulty performing the exercises. The patient states that his arms "feel like jelly after just a few repetitions." He also has severe muscle cramping and has noticed occasional urine discoloration after training sessions. Further evaluation reveals that the patient's exercise tolerance can be greatly improved by drinking an oral glucose solution before beginning a strenuous activity. Vital signs are normal, and examination is unremarkable. This patient is most likely deficient in an enzyme that catalyzes which of the following conversions?

Question

A 15-year-old boy is brought to the clinic due to poor exercise endurance.  He recently began weight lifting with friends but has had difficulty performing the exercises.  The patient states that his arms "feel like jelly after just a few repetitions."  He also has severe muscle cramping and has noticed occasional urine discoloration after training sessions.  Further evaluation reveals that the patient's exercise tolerance can be greatly improved by drinking an oral glucose solution before beginning a strenuous activity.  Vital signs are normal, and examination is unremarkable.  This patient is most likely deficient in an enzyme that catalyzes which of the following conversions?

Quizplus · Accepted Answer

11ec160b_36a3_36db_9249_15d2c9328a97_MD0001_00 This patient most likely has McArdle disease (glycogen storage disease type V). This condition is caused by a deficiency of myophosphorylase, an isoenzyme of glycogen phosphorylase present in muscle tissue. Deficiency leads to decreased breakdown of glycogen during exercise, resulting in poor exercise tolerance, muscle cramps, and rhabdomyolysis (eg, red urine). The prognosis is generally good, and symptoms can be improved by consuming simple sugars before beginning physical activity. During glycogenolysis, glycogen phosphorylase shortens glycogen chains by cleaving 1,4-alpha-glycosidic linkages between glucose residues, liberating glucose-1-phosphate in the process. This occurs until 4 residues remain before a branch point (the limit dextrin). At this point, the debranching enzyme performs 2 enzymatic functions: Glucosyltransferase cleaves the 3 outer glucose residues of the 4 that are left by glycogen phosphorylase and transfers them to a nearby branch The enzyme alpha-1,6-glucosidase removes the single remaining branch residue, producing free glucose and a linear glycogen chain that can be further shortened by glycogen phosphorylase (Choice B) Glucose-1-phosphate generated by glycogenolysis is converted by phosphoglucomutase to glucose-6-phosphate. Unlike myophosphorylase, phosphoglucomutase is present in both skeletal muscle and liver. Phosphoglucomutase deficiency is extremely rare, presenting with muscle weakness and fasting hypoglycemia. (Choice C) Glucose-6-phosphate is converted to 6-phosphogluconate through a series of reactions by glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase in the pentose phosphate pathway. This pathway maintains adequate levels of reduced glutathione, which is needed to protect from oxidative injury (eg, prevent red cell hemolysis). (Choice D) Glucose-6-phosphate is converted to fructose-6-phosphate by glucose-6-phosphate isomerase during glycolysis. A deficiency here would disrupt glycolysis, affecting cells that rely on it as their energy source (eg, red blood cells). Patients have chronic hemolytic anemia. (Choice E) Within the liver and kidney, glucose-6-phosphatase converts glucose-6-phosphate to glucose to help maintain blood glucose levels during fasting. A deficiency here leads to glycogen storage disease type I (von Gierke disease), presenting in infancy with hypoglycemia. Educational objective: Myophosphorylase deficiency (McArdle disease, or glycogen storage disease type V) causes failure of muscle glycogenolysis, resulting in decreased exercise tolerance, muscle pain, cramping, and myoglobinuria shortly after initiating physical activity.

A 15-Year-Old Boy Is Brought to the Clinic Due to Poor