McArdle Disease (Type V Glycogen Storage Disease) Flashcards
A 20-year-old man reports muscle pain, cramping, and fatigue shortly after starting exercise, especially with high-intensity activities. He describes that his symptoms improve after a few minutes of rest or slower activity. On further questioning, he recalls episodes of dark-colored urine following strenuous exercise. Physical examination reveals no muscle atrophy. Exercise testing shows a flat venous lactate curve with elevated blood ammonia levels. Genetic testing identifies a mutation in the PYGM gene. Which of the following best explains the pathophysiology of this condition?
A) Impaired transport of glucose into muscle cells
B) Defective breakdown of glycogen into glucose-1-phosphate in skeletal muscle
C) Impaired mitochondrial oxidative phosphorylation
D) Deficiency of lysosomal acid maltase
E) Impaired glycolysis due to phosphofructokinase deficiency
Answer: Defective breakdown of glycogen into glucose-1-phosphate in skeletal muscle
Explanation: McArdle disease is caused by a deficiency of myophosphorylase, an enzyme responsible for breaking down glycogen into glucose-1-phosphate for energy production in skeletal muscles. This deficiency leads to the accumulation of glycogen in muscle cells, exercise intolerance, and muscle cramps. The “second wind phenomenon,” where symptoms improve after a few minutes of reduced activity, occurs due to increased blood flow and alternative energy sources. A flat venous lactate curve during exercise and elevated blood ammonia levels are hallmark diagnostic findings.
Incorrect Answers:
A) Impaired glucose transport is seen in GLUT-1 deficiency syndrome, not McArdle disease.
C) Impaired mitochondrial oxidative phosphorylation occurs in mitochondrial myopathies, which present with lactic acidosis.
D) Lysosomal acid maltase deficiency causes Pompe disease, leading to cardiomyopathy and hypotonia.
E) Phosphofructokinase deficiency causes Tarui disease, characterized by hemolysis in addition to muscle symptoms.
What is the primary mode of inheritance for McArdle disease?
Autosomal recessive inheritance
When does McArdle disease (Type V glycogen storage disease) present?
during adolescence.
What is the gene defect and deficient enzyme in McArdle disease (Type V glycogen storage disease)?
Mutation in the PYGM gene on chromosome 11q; deficient enzyme is myophosphorylase (skeletal muscle glycogen phosphorylase)
What is the role of myophosphorylase in McArdle disease?
Breaks down glycogen into glucose-1-phosphate for energy production in skeletal muscles
What are the characteristic muscular symptoms of McArdle disease?
Generalized muscle weakness, exercise intolerance, and muscle fatigue
What is the ‘second wind phenomenon’ seen in McArdle disease?
Symptoms of muscle fatigue disappear after a period of rest or slower activity due to increased muscular blood flow
What metabolic abnormalities are observed during exercise in McArdle disease?
Flat venous lactate curve with exaggerated elevations in blood ammonia during exercise
Why does exercise in McArdle disease sometimes lead to myoglobinuria?
Demanding physical exercise causes muscle damage and release of myoglobin into the bloodstream
What are the laboratory findings in McArdle disease during exercise testing?
Normal serum glucose levels and no rise in lactate during exercise.
Elevated blood ammonia.
What lifestyle modifications are recommended for McArdle disease management?
- Low-intensity exercise.
- Adequate carbohydrate intake before exercise.
- Avoidance of strenuous activity.
