1. Background

• myophosphorylase is an enzyme in the glycogenolytic pathway which helps convert glycogen to lactate by disrupting the 1,4 linkages between glycosyl units
• in McArdle Disease:
  • phosphorylase activity in liver & smooth muscle is normal
  • the phosphorylase activity appears to be lost in muscle fibres as they mature
  • the phosphorylase-activating system is intact
  • with normal activity, energy for muscle contraction is provided by glucose uptake by the muscle fibres but the energy for strenuous muscle contractions cannot be supplemented by the breakdown of stored muscle glycogen causing pain and cramping with little or no lactic acid production

2. Genetic Defect

• genetic defect -> deficiency of myophosphorylase activity -> decline in glucose-1-phosphate and, subsequently, lactate production

1. Muscle Biopsy

1. Musculoskeletal Manifestations

• decreased stamina and fatiguability
• exercise intolerance
• muscle pain and stiffness
  • with minimal to vigorous exercise
  • abates with cessation of exercise
  • associated with prolonged (1-2 days) muscle pain and swelling with prolonged exercise
  • primarily affects distal muscles
• slowly progressive muscle atrophy and weakness in adolescence and early adulthood
• normal mental development

2. Complications (with prolonged vigorous exercise)

• gross myoglobinuria due to rhabdomyolysis resulting in
  • acute renal failure (for acute episodes)
  • chronic renal failure (for prolonged or frequent repetitive episodes of myoglobinuria)
• syncope
• seizures
• there may be an infantile form characterized by:
  • severe infantile hypotonia and weakness
  • poor prognosis

1. Ischemic Exercise (Lactate) Test

• inflation of blood pressure cuff to above arterial pressure
• patient squeezes a rubber ball every second
• normal persons:
  • can squeeze 70-110x before some discomfort
  • venous samples from the arm will show a rise in lactate
• affected persons:
  • can only squeeze 20-30x due to muscle cramps which persist after the cuff is released with the hand held in a tetanic position (wrist bent, fingers extended)
  • cramp resolves after a few minutes but the pain may persist for days
  • venous samples from the arm do not show a rise in lactate
  • MRI will demonstrate a sharp fall in creatine phosphate and pH and a rise in inorganic phosphate
  • EMG will show no electrical activity within the contracted muscle

2. Serum

• elevated CPK after strenuous exercise
• BUN, creatinine, uric acid

3. Muscle Biopsy Biochemistry

• decreased myophosphatase activity

4. Urine

• myoglobinuria after moderate or strenuous exercise

1. Supportive

• no treatment for disease
• a fat- or protein-rich diet may increase tolerance to submaxiaml exercise and increase recovery time
• genetic counselling

2. Prognosis

• good but may become debilitating in later years