NATURAL HISTORY OF LGMD2A FOR DELINEATING OUTCOME MEASURES IN CLINICAL TRIALS
Isabelle Richard, Jean Yves Hogrel , Daniel Stockholm et al
Annals of Clinical and Translational Neurology
2016; 3 (4): 248-265
INTRODUCTION
Girdle muscular dystrophy type LGMD2A (LGMD2A, OMIM) is a slowly progressive myopathy caused by deficiency of calpain 3, a calcium-dependent protease of skeletal muscle.
METHODS
We conducted an observational study of clinical manifestations and disease progression over 4 years in patients with genetically confirmed LGMD2A . A total of 85 patients, aged 14-65 years, were recruited from 3 centers located in metropolitan France, the Basque region and Reunion Island. They were followed up every 6 months for 2 years, and a subgroup was evaluated annually for another 2 years thereafter.
Data collected from all patients included medical history, hematochemical parameters, muscle strength measurement by manual muscle testing (MMT) and quantitative muscle testing, motor functional assessments and cardiac and respiratory function. In a subgroup of patients, a Computed Tomography of the lower limbs was also performed.
RESULTS
Our study confirms the cynical description of a slowly progressive muscle disorder with onset in the first or second decade of life with a certain degree of variability related to sex and mutation type. Null mutations cause a more severe phenotype while patients carrying compound heterozygotes are less severely affected
Muscle weakness is symmetrical and prevalent in the axial muscles of the trunk and proximal lower limbs. A high correlation is evident between the level of muscle impairment tested by MMT and the loss of density on analysis by computed tomography.
INTERPRETATION
All data produced will help determine endpoints for possible future studies.