PMC4188961_01
PMC4188961_02
Computed tomography of the pelvis, thighs and legs. At the pelvis there is advanced gluteus maximus, gluteus medius, and gluteus minimus involvement. At the thigh, there is advanced biceps femoris, semitendinosus, semimembranosus involvement; severe vastus lateralis, vastus medialis, vastus intermedius, and adductor magnus involvement, with relative preservation and hypertrophy of sartorius and gracilis. At the leg, there is asymmetric muscle involvement with advanced right gastrocnemius medialis, left peroneus, bilateral soleus involvement, compared to tibialis anterior muscle sparing.
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PMC4188961_02_1472-6890-14-41-1.jpg
F1
At the leg, there was asymmetric muscle involvement with advanced (grade 4) soleus, right gastrocnemius medialis, and left peroneus involvement, as well as tibialis anterior muscle sparing (Figure 1).Patient was submitted, when he was 31 years old, to a left vastus lateralis muscle biopsy that demonstrated abnormal architecture with areas of fibrous and fat replacement, endomysial fibrosis, fiber splitting, atrophic and hypertrophic fibers.
Muscle biopsy. (A) Severe variation in fiber calibre, showing groups of atrophic fibers (arrow) and groups of hypertrofic fibers (HE 100x). (B) Frequent rimmed vacuoles (arrows) with basophilic material (HE 400x). (C) Immunohistochemical reaction with complete telethonin deficiency. Inset presents strong normal sarcolemmal reaction in control muscle (Antibody anti-telethonin (G-11): sc-25327, Santa Cruz Biotechnology, Inc., at 1:50 dilution). (D, E, F) Serial frozen sections of the same muscle fibers (arrows) showing irregular dystrophin carboxy-terminus reaction (E) (D - Rod-domain anti-dystrophin antibody (NCLDYS1 Novocastra at 1:20 dilution), E - Carboxy-terminus anti-dystrophin antibody (NCLDYS2 Novocastra at 1:20 dilution), F - Amino-terminus anti-dystrophin antibody (NCLDYS3 Novocastra at 1:20 dilution), (G) Muscle tissue shows autophagic vacuoles (arrows) with membrane debris and myelinoid figures (transmission electron microscopy 5000x), (H) Atrophic muscle fiber with myofibrillar disorganization, and few residual sarcomeres with distinguishable Z lines (arrows) (transmission electron microscopy 6000x).
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PMC4188961_02_1472-6890-14-41-2.jpg
F2
There were groups of atrophic and groups of hypertrophic fibers (Figure 2A), with type 2 fiber predominance (data not shown). Rimmed vacuoles were characterized by empty spaces with a rim of basophilic material (Figure 2B). Immunohistochemical studies for the three dystrophin epitopes (Rod, carboxy-terminus, amino-terminus), disclosed focal irregular reaction for the carboxy-terminus that was evident on serial sections of the same fibers (Figure 2D,E,F). Immunohistochemical reaction for the anti-telethonin antibody showed total deficiency (Figure 2C), consistent with telethoninopathy (Limb Girdle Muscular Dystrophy type 2G).Transmission electron microscopy demonstrated endomysial fibrosis, fiber and myofiber splitting, focal intrasarcoplasmic glycogen deposits, many degenerating fibers, very small atrophic fibers with or without degeneration signs, and autophagic vacuoles with numerous membrane and sarcoplasmic debris (Figure 2G,H).