Case Study 84Leonidas Arvanitis, MD

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

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

Question 2:

• Based on the most likely diagnosis what would an ATPase stain show?

Answer 2:

• Type 1 fiber predominance

Question 3:

• Would electron microscopy be helpful?

Answer 3:

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

Question 4:

• What is your diagnosis?

Answer 5:

• Central core myopathy

Question 6:• Central core myopathy is caused by

mutations in which gene?

a. RYR1 encoding Ryanodine receptor

b. SEPN1 encoding Selenoprotein N1

c. NEB encoding Nebulin

d. MTM1 encoding Myotubalarin

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

RYR1 gene

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

Question 7:

• What other condition is the same gene responsible for?

Answer 7:

• Malignant hyperthermia