Figure 2.

Histopathological Findings in PYROXD1 Myopathy

(A) Histopathological findings in skeletal muscle sections from family A (A-II1, quadriceps biopsy at 11 years of age), family B (B-II3, quadriceps biopsy at 16 years of age), and family C (C-II2, quadriceps biopsy at 4 years of age). Haemotoxylin and eosin (H&E) staining of muscle biopsy specimens from each family shows variation in fiber size, multiple internalized nuclei, and increased fibrous connective tissue. Immunofluorescent staining of skeletal muscle from A-II1 and C-II2 and immunoperoxidase staining from B-II3 demonstrate inclusions highly immunoreactive to desmin, myotillin, and alpha-actin (and αB-crystallin, not shown). H&E and immunoperoxidase images are provided via Hospital Pathology without a scale bar. Fibers in sequential sections of B-II3 are marked with a yellow star.

(B) Electron microscopy of muscle biopsy specimens. Family A: (i) small atrophic fiber with a central nucleus and loss of sarcomeric organization; (ii) large region of Z-band streaming with only occasional areas of normal sarcomeric register; and (iii, iv) atrophic fibers showing total loss of sarcomeric register, loss of thick filaments, and prominent Z-bands sometimes forming small nemaline bodies. Family B: (v) Large fibers show large central minicore-like regions devoid of normal myofibrillar structure and lacking mitochondria and organelles, with adjacent small fibers showing total loss of sarcomeric structure, accumulations of thin filaments, and loss of thick filaments; (vi) many large fibers have multiple internalized nuclei, often in clusters; and (vii) fibers show thin filament accumulations with electron-dense aggregates that resemble thickened z-lines and small nemaline bodies. Family C: (viii) Small atrophic fiber with loss of sarcomeric register. A large fiber shows multiple areas of Z-band streaming and a minicore-like region with absence of normal myofibrillar structure.