Case Study 84 Leonidas Arvanitis, MD

1. Case Study 84Leonidas Arvanitis, MD

2. Question 1: • A 60 year old male presents with generalized muscle weakness • Describe the histologic findings on the H&E and NADH stains • Click here to view H&E and NADH stains

3. Answer 1: • H&E stained frozen sections • Abnormal variation in myofiber sizes (25-100 microns) • Excess of internalized nuclei • Degenerating or regenerating fibers or inflammatory infiltrates are not seen • NADH-TR reacted sections • One or two central or eccentric cores in the vast majority of fibers. • On longitudinal section the cores traverse the length of the fiber. • No target fibers are seen • The cores involve primarily type 1 fibers

4. Question 2: • Based on the most likely diagnosis what would an ATPase stain show?

5. Answer 2: • Type 1 fiber predominance

6. Question 3: • Would electron microscopy be helpful?

7. Answer 3: • Yes. It would reveal the absence of mitochondria and sarcoplasmic reticulum in core regions

8. Question 4: • What is your diagnosis?

9. Answer 5: • Central core myopathy

10. Question 6: • Central core myopathy is caused by mutations in which gene? • RYR1 encoding Ryanodine receptor • SEPN1 encoding Selenoprotein N1 • NEB encoding Nebulin • MTM1 encoding Myotubalarin

11. Answer 6: • Central core myopathy is caused by mutations in which gene? • RYR1 encoding Ryanodine receptor • SEPN1 encoding Selenoprotein N1 • NEB encoding Nebulin • MTM1 encoding Myotubalarin

12. RYR1 gene • RYR1 gene encodes for the protein ryanodine receptor, which is a ligand-gated release channel for Ca²´ stored in the terminal cisterna

13. Question 7: • What other condition is the same gene responsible for?

14. Answer 7: • Malignant hyperthermia