Background: Limb girdle muscular dystrophy type 2A (LGMD2A) is characterized by a wide range of clinical variability and rate of progression. Patients with two null mutations usually have a rapid course, but in the remaining cases (two missense mutations or compound heterozygote mutations) no prognostic indices are available.
Materials and methods: We conducted the first systematic investigation at the histopathological, biochemical and molecular level of 24 LGMD2A patients, subdivided according to rapid or slow disease progression, to determine if some parameters could correlate with disease progression.
Results: We have demonstrated that muscle histopathology score and the extent of regenerating and degenerating fibers could correlate with the rate of disease course when the biochemical and molecular data do not offer enough information. Comparison of clinical and muscle histopathological data between LGMD2A and 4 different types of LGMD (LGMD2B, 2C, 2D, 2E) also gave another important and novel result. We have shown that LGMD2A has significantly lower levels of dystrophic features (i.e. degenerating and regenerating fibers) and higher degree of chronic changes (i.e. lobulated fibers) when compared with other LGMDs, particularly LGMD2B. These results might explain the clinical observation that atrophic muscle involvement seems to be a clinical feature peculiar to LGMD2A patients.
Conclusions: Distinguishing patterns of muscle histopathological changes in LGMD2A might reflect the effects of a disease-specific pathogenetic mechanism and provide clues complementary to genetic data.
- limb-girdle muscular dystrophy
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