282nd ENMC international workshop: Standard of diagnosis and care for the sarcoglycanopathies

Topic:

Clinical Management

Poster Number: P220

Author(s):

Megan A. Iammarino, Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OH, USA, Meredith James, PT, PhD, The John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS, Laura Cardenas, Proyectoalpha, Carles Sanchez, GFB Onlus Organization, Claudio Bruno, Instituto Giannina Gaslini Genova, Kristl Claeys, University Hospital Leuven, Leonela Luce, Newcastle University, Nicholas Johnson, Virginia Commonwealth University, Lea Leonardis, Ljubljana Medical Centre, Marta de Antiono Ferrer, Hospital Sant Pau , Dorianna Sandona, University of Padova, Beril Talim, Hacettepe University, Isabelle Richard, AtaMyo, Giorgio Tasca, MD, PhD, Newcastle University, Najoua Miladi, Tunesia, Conrad Weihl, MD, PhD, Washington University, Stephan Wenninger, Ludwig Maximilians University of Munich, Felipe di Pace, Brazil, Andre Muller-York, Sarepta Therapeutics, Suji Vasu, LGMD2D Foundation, Aleksandra Leijenhorst Le Belle, Stichting SpierKracht/ LGMD CAB, Holly Borland, Newcastle University, Jorge Alonso-Perez, Newcastle University, Elena Pegoraro, PhD, University of Padova, Tanya Stojkovic, Institut de Myologie - Hôpital Pitié-Salpêtrière, Linda Lowes, Nationwide Children's Hospital, Jordi Diaz-Manera, MD, John Walton Muscular Dystrophy Research Centre

Background: The 282nd European Neuromuscular Center (ENMC) International Workshop on the diagnosis and management of the sarcoglycanopathies (LGMDR3,R4,R5,&R6) was held on November 8-10, 2024. In attendance were 29 stakeholders from 12 countries, including multidisciplinary experts in the fields of basic science, translational research, and clinical care, industry representatives, and participation from patients and patient advocacy groups.
Objective: The focus of this workshop was to align experience from around the world, provide data-driven recommendations for the clinical care of individuals with the diagnosis of a sarcoglycanopathy, and identify unmet needs.
Results: With variable access to next generation sequencing, a diagnostic algorithm was proposed, including common clinical presentations, differential diagnoses, and presentation of immunohistochemistry and magnetic resonance imaging results including patterns of muscle involvement across subgroups. Cardiac and respiratory manifestations were variable. Onset of respiratory complications were primarily seen when ambulation is lost, while cardiomyopathy was noted prior to this; monitoring for cardiac and pulmonary function was recommended throughout the disease course. To harmonize the stratification of clinical data across countries and clinics, a standardized definition of ‘ambulatory’ was proposed; the ability to complete the 10-meters, without orthotics or assistive device, in <30 seconds. Recommendations for a gold standard set of clinical outcome assessments and frequency of monitoring was proposed, along with a corresponding minimum acceptable dataset. Due to the heterogeneity of the sarcoglycanopathies, our goal was to capture a more robust understanding of clinical trajectories across variants and subtypes to further inform future care and clinical trial design. Additional topics included recommendations for exercise, anesthesia & emergency care, and transitional care from pediatric to adult facilities, clinical trial opportunities, and drug discovery programs. Endocrinological and nutritional aspects of these diagnoses were identified as areas that would benefit from further understanding, in addition to further facilitating interactions between health care providers, researcher scientists, and patient advocacy organizations. Conclusions: Alignment in diagnosis, care, and documentation is crucial for further understanding of the clinical trajectories of the sarcoglycanopathies.