Age-associated reductions in functional muscle mass in DMD: Cross-sectional measurements with D3creatine dilution in patients aged 4 – 24 years

Topic:

Translational Research

Poster Number: S74

Author(s):

William Evans, PhD, University of California, Berkeley, Mahalakshmi Shankaran, PhD, University of California, Berkeley, Marc Hellerstein, MD, PhD, University of California, Berkeley, Russell Butterfield, MD, PhD, University of Utah, Edward Smith, MD, Duke University, Michela Guglieri, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Natalie Katz, MD, PhD, Duke University Medical Center, Brittany Nave, Duke University, Kalista Vordos, University of Utah, Laura Behar, RN, Newcastle Hospitals NHS Foundation Trust, Meredith James, BAppSci, Newcastle Hospitals NHS Foundation Trust

The D3Creatine (D3Cr) dilution method is an accurate, non-invasive measurement of functional muscle mass (MM). This is a multi-center study of functional MM in DMD patients aged 4 – 24 years. Participants ingested 20 mg of D3Cr dissolved in water and collected a fasting urine sample 2 and 3 days later for analysis of D3creatinine enrichment. The Northstar Ambulatory Assessment (NSAA) total score for ambulatory participants and the Performance of Upper Limb (PUL 2.0) total score for all participants. We describe a cross-sectional examination of MM in 86 subjects (45 non-ambulant). We observed a striking age-associated reduction in %functional MM (r = -0.6491, p < 0.0001) and functional MM. Age (years),Body Weight (kg), Muscle Mass (kg)% Muscle Mass: 4-7 years (n=12), 26.7 ± 10.7 (n=12),7.1 ± 2.0 (n=12),27.9 ± 5.6 (n=12) 8-12 years (n=27), 49.9 ± 18.7 (n=26)*,10.6 ± 4.3 (n=27)*†,22.9 ± 8.6 (n=26)† 13-17 years (n=23),62.4 ± 19.8 (n=23)*,10.1 ± 3.4 (n=23)*†,17 ± 6.5 (n=23) *†‡ 18-24 years (n=24), 63.2 ± 22.3 (n=23)*,6.3 ± 3.1 (n=24),11 ± 6.8 (n=23)* *p<0.05 vs. 4-7 years, †p<0.05 vs. 18-24 years, ‡p<0.05 vs. 9-12 years The age-associated decrease in MM was strongly associated with functional status (ambulatory vs non-ambulatory). Ambulant vs non-ambulant: Age 10.4 ± 3.7 vs. 17.2 ± 4.4 years, p<0.0001; body weight 41.74 ± 17.3 vs. 64.5 ± 21.6 kg p<0.0001; MM 10.4 ± 4 vs. 7.3 ± 3.2 kg, p<0.0005; and %MM 26.1 ± 6.2 vs. 12.0 ± 5.5 % p<0.000. MM and %MM were strongly associated with PUL score (r = 0.515, p<0.0001 and r=0.782, p<0.0001 respectively). The study suggests that D3Cr dilution provides a simple, non-invasive assessment of MM for patients with DMD, across a wide age and functional status range.