Muscle pathology in 31 patients with calpain 3 gene mutations..

BACKGROUND AND PURPOSE: At present, more than 20 different forms of limb-girdle muscular dystrophies (LGMDs) are known (at least 7 autosomal dominant and 14 autosomal recessive). Although these different forms show some typical phenotypic characteristics, the existing clinical overlap makes their differential diagnosis difficult. Limb-girdle muscular dystrophy type 2 (LGMD2A) is the most prevalent LGMD in many European as well as Brazilian communities and is caused by mutations in the gene CAPN3. Laboratory testing, such as calpain immunohistochemistry and Western-blot analysis, is not totally reliable, since up to 20% of molecularly confirmed LGMD2A show normal content of calpain 3 and a third of LGMD2A biopsies have normal calpain 3 proteo-lytic activity in the muscle. Thus, genetic testing is considered as the only reliable diagnostic criterion in LGMD2A. MATERIAL AND METHODS: In an attempt to find a correlation between genotype and muscle pathology in limb-girdle muscular dystrophy 2A we performed histopathological investigation of a group of 31 patients subdivided according to the type of pathologic CAPN3 gene mutation. RESULTS: In all biopsies typical features of muscular dystrophy such as fiber necrosis and regeneration, variation in fiber size and fibrosis were noted. Lobulated fibers were often encountered in the muscle biopsies of LGMD2A patients. Such fibers were more frequent in patients with 550delA mutation. CONCLUSIONS: These findings may be helpful in establishing diagnostic strategies in LGMD.

Myopathy associated with sclerodermal facial hemiatrophy.

A patient who had linear scleroderma associated with ipsilateral hemiatrophy of the tongue and subsequent facial hemiatrophy was studied. Biopsy specimens of the plaque of scleroderma showed the skin changes of scleroderma as well as fascial and muscle changes. The fascia had an impressive plasma cell fasciitis with numerous plasma cells and scattered lymphohistiocytic cells. Histochemical study of the temporalis muscle underlying the plaque of circumscribed scleroderma disclosed severe localized atrophy of type 1 and type 2 fibers similar to the pathologic findings previously described in a patient with localized scleroderma.

Occurrence of alkaline phosphatase-positive fibers in experimental muscle disorders.

The alkaline phosphatase (AP) reaction was carried out on muscle sections from a large series of rats under various experimental neuromuscular disorders. Only denervated and non-innervated muscle fibers stained positively with the AP reaction. In other conditions including degenerating, regenerating, tenotomized and immature muscles the AP reaction was negative. This suggests that the presence of AP-positive fibers in human neuromuscular disorders reflects a concomitant denervation process.

Familial inclusion body myopathy with desmin storage.

We report two adult familial cases of inclusion body myopathy (IBM) with desmin storage in skeletal muscle. Clinically, both patients presented late-onset, progressive, symmetrical, both proximal and distal muscle weakness. Muscle biopsy findings were identical in both cases and consisted of marked variability in fiber size, increased number of central nuclei and vacuolation involving 10% of fibers. Single or multiple vacuoles were located subsarcolemmally or in the center, and were rimmed by basophilic material. At the ultrastructural level, tubulofilamentous nuclear and cytoplasmic inclusions of 16-21 nm in diameter were frequently observed. In addition, large subsarcolemmal and central deposits composed of electron-dense granular material were present in many fibers. Immunocytochemistry revealed staining for desmin, vimentin and ubiquitin within both inclusions and vacuolated fibers. Possible structural and functional associations between these two types of muscle changes remain unclear. They may either represent two coexistent disease processes or merely reflect an abnormal form of muscle fiber degradation, with unidentifiable specificity.