1. Case Study 84 Leonidas 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 NADH-TR reacted sections
Abnormal variation in myofiber sizes ( 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