DMD – CLINICAL CARE: EP.101 Appendicular lean mass index (ALMI) changes in patients with dystrophinopathies

Abstract

The musculo-skeletal phenotype of patients with dystrophinopathies range from Severe DMD with loss of ambulation (LOA) before age 13 years, to Intermediate DMD with LOA between 13 to 16 years and asymptomatic patients with Becker muscular dystrophy (BMD). Compared to healthy controls, we found that males with DMD have progressive decline in Appendicular Lean Mass Index (ALMI) with age and with worsening functional mobility. The age-related trajectories of ALM/ALMI in pediatric patients with BMD and Intermediate DMD have not yet been characterized. We aimed to: (1) compare ALM/ALMI of pediatric male patients with DMD in different stages of disease with that of patients with BMD; (2) compare ALM trajectories of patients with Intermediate DMD and BMD with those of typical DMD; and (3) compare ALM trajectories by the 4 DMD genotypes – mutations in exons 1-30, 31-44, 45 – 62 and 63-79. We conducted a retrospective longitudinal study of 499 patients (ages 2 – 20 y) with DMD (466 typical DMD; 33 DMD Intermediate) and 46 patients with BMD and normal motor function. ALM and ALMI (kg/m2) were measured by dual energy X-ray absorptiometry (DXA). ALM and ALMI from 693 healthy male controls were used as a reference to calculate age-specific Z-scores. Results: Mean ALMI Z-scores of DMD patients fell below -2 around age 12y while that of BMD patients remained within ± 2 without decline. ALMI of DMD patients declined after age 10 y while BMD patients accrued ALM but at a slower rate than healthy controls. ALMI started to decline in the milder Intermediate DMD patients around age 14 y. DMD patients with mutations in exons 63-79 appear to have greater declines in ALMI after age 10 y than DMD patients with the other 3 genotypes. Our data on ALMI trajectories in pediatric patients with dystrophinopathies can provide insight for clinical care management needs as well as inform clinical trial design for therapeutic trials in DMD and BMD.