Case Study 84 Leonidas 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 NADH-TR reacted 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? RYR1 encoding Ryanodine receptor SEPN1 encoding Selenoprotein N1 NEB encoding Nebulin 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