Clinical Determinants of Disease Progression in Patients With Beta-Sarcoglycan Gene Mutations.

Background

Limb-girdle muscular dystrophy 2E (LGMD 2E), recently renamed as autosomal recessive limb-girdle muscular dystrophy-4 (LGMDR4), is characterized by the lack of beta-sarcoglycan, normally expressed in skeletal muscles and cardiomyocytes. We hypothesized that progressive respiratory and left ventricular (LV) failure in LGMDR4 could be associated with the age and interrelated phenomena of the disease's natural history.

Methods

We conducted a retrospective review of the records of 26 patients with LGMDR4. Our primary objective was to compare the rates of decline among creatine phosphokinase (CPK) values, pulmonary function test (PFT) measures, and echocardiographic estimates and to relate them to patients' age.

Results

The rates of decline/year of CPK, PFTs, and LV function estimates are significatively bound to age, with the LV ejection fraction (EF) being the strongest independent variable describing disease progression. Moreover, the rate of decline of CPK, PFTs, and LV differed in patients grouped according to their genetic mutations, demonstrating a possible genotype-phenotype correlation. The parallel trend of decline in CPK, PFT, and EF values demonstrates the presence in LGMDR4 of a simultaneous and progressive deterioration in muscular, respiratory, and cardiac function.

Conclusions

This study expands the current knowledge regarding the trend of CPK values and cardiac and respiratory impairment in patients with LGMDR4, to optimize the monitoring of these patients, to improve their quality of life, and to provide clinical indices capable of quantifying the effects of any new gene or drug therapy.