What stain can be used to diagnose the primary muscle disorder in a patient with suspected McArdle disease (Glycogen Storage Disease)?

Periodic Acid-Schiff (PAS) Stain for Diagnosing McArdle Disease

The Periodic acid-Schiff (PAS) stain is the most appropriate stain for diagnosing McArdle disease (glycogen storage disease type V) in this patient with exercise intolerance, muscle pain, elevated creatine kinase, and abnormal forearm ischemic test.

Pathophysiology and Clinical Presentation

McArdle disease is an autosomal recessive metabolic disorder characterized by:

• Deficiency of muscle glycogen phosphorylase (myophosphorylase, PYGM)
• Complete inability to break down glycogen in skeletal muscle
• Exercise intolerance with early fatigue
• Muscle cramps and pain during exercise
• Risk of rhabdomyolysis with intense exercise

The patient's presentation is classic for McArdle disease:

• Long-standing exercise intolerance
• Muscle pain and cramps during exertion
• Elevated creatine kinase after exercise
• Abnormal forearm ischemic test showing lack of lactate and pyruvate elevation

Diagnostic Approach for Muscle Biopsy

Why PAS is the Correct Choice:

1. PAS staining characteristics in McArdle disease:

   • Shows excessive glycogen accumulation in muscle fibers
   • Demonstrates PAS-positive material in the cytoplasm 1
   • The stored glycogen is diastase-sensitive (will disappear after diastase treatment)

2. Diagnostic confirmation:

   • PAS staining reveals abnormal glycogen accumulation
   • When combined with the absence of myophosphorylase activity, confirms McArdle disease
   • The glycogen content is extremely elevated (3-5 times normal levels) 1, 2

Why Other Stains Are Not Optimal:

• Masson's trichrome: Primarily used to identify fibrosis and connective tissue; not specific for glycogen detection
• Hematoxylin and eosin (H&E): Basic stain that may show vacuoles but doesn't specifically identify glycogen
• Congo red: Used to identify amyloid deposits, not relevant for glycogen storage diseases

Diagnostic Algorithm for McArdle Disease

1. Clinical suspicion based on exercise intolerance and muscle cramps
2. Laboratory findings:
   • Elevated CK (especially post-exercise)
   • Normal lactate response to exercise
   • Abnormal forearm ischemic test (lack of lactate rise)
3. Muscle biopsy with PAS staining:
   • Shows excessive glycogen accumulation
   • PAS-positive, diastase-sensitive material
4. Enzyme analysis:
   • Confirms deficiency of myophosphorylase activity
5. Genetic testing:
   • Identifies mutations in the PYGM gene

Importance of Proper Tissue Handling

When performing a muscle biopsy for suspected glycogen storage disease:

• Great care must be taken not to wash out glycogen during processing 1
• Tissue should be snap-frozen in liquid nitrogen for biochemical analysis
• 30-40 mg of tissue is typically required for comprehensive studies 1
• Both histological and biochemical analyses should be performed

Clinical Management Considerations

Once diagnosed, management focuses on:

• Moderate-intensity exercise with pre-exercise carbohydrate ingestion 3
• Regular physical activity to attenuate clinical severity 3
• Avoiding intense exercise that could trigger rhabdomyolysis
• Monitoring for complications such as acute renal failure 4

Distinguishing from Other Glycogen Storage Diseases

McArdle disease must be differentiated from other glycogen storage diseases:

• GSD III (debrancher deficiency): Has liver involvement and different glycogen structure
• GSD II (Pompe disease): Shows lysosomal glycogen on histology and affects respiratory muscles 1
• GSD IV: Has abnormal glycogen structure (amylopectin-like) 1

The combination of clinical presentation, forearm ischemic test results, and PAS-positive/myophosphorylase-negative muscle biopsy findings is diagnostic for McArdle disease.