The objectives of this study were threefold: i) to better define the clinical characteristics of a large group of patients with confirmed calpainopathy, ii) to describe the profile and degree of muscle weakness as well as the various modalities of disease progression, and iii) to select outcome measures for future clinical trials. The authors thus carried out an observational study of clinical manifestations and disease progression in genetically confirmed Limb-girdle muscular dystophy 2A (LGMD2A, OMIM) patients for up to 4 years. A total of 85 patients, aged 14-65 years, were recruited in three centers located in metropolitan France, the Basque country, and the Reunion Island. They were followed up every 6 months for 2 years and a subgroup was assessed annually thereafter for two more years. Data collected for all patients included clinical history, blood parameters, muscle strength assessed by manual muscle testing (MMT) and quantitative muscle testing, functional scores, and pulmonary and cardiac functions. In addition, CT scans of the lower limbs were performed in a subgroup of patients. This study confirms the clinical description of a slowly progressive disorder with onset in the first or second decade of life with some degree of variability related to gender and mutation type. The null mutations lead to a more severe phenotype while compound heterozygote patients are the least affected. Muscle weakness is remarkably symmetrical and predominant in the axial muscles of the trunk and proximal muscles of the lower limb. There was a high correlation between the weakness at individual muscle level as assessed by MMT and the loss of density in CT scan analysis.
