282nd ENMC international workshop - standards of diagnosis and care for the sarcoglycanopathies. 8-10 November 2024,...

Sarcoglycanopathies are rare autosomal recessive limb-girdle muscular dystrophies (LGMD R3-R6) caused by pathogenic variants in SGCA, SGCB, SGCG, or SGCD genes. They present predominantly in childhood with progressive proximal muscle weakness, frequently leading to loss of ambulation in adolescence or early adulthood, and may involve cardiac and respiratory complications. Despite their severity and multisystem impact, no internationally agreed standards of care (SoC) currently exist, contributing to diagnostic delays, inconsistent management, and inequitable access to multidisciplinary expertise. The 282nd ENMC International Workshop (Amsterdam, November 2024) convened 29 global stakeholders including clinicians, researchers, industry, and patient representatives to harmonize literature evidence with international clinical experience. Key outputs included: consensus on the clinical spectrum and diagnostic algorithm (with and without genetic testing); recommendations for multidisciplinary management covering neurology, cardiology, respiratory care, rehabilitation, and psychosocial support; and identification of outcome measures for clinical monitoring and trials. Natural history data were reviewed to define prognostic factors, and emerging therapeutic avenues including gene therapy, small-molecule correctors, and antifibrotic strategies were discussed. The workshop concluded with a mandate to develop and disseminate comprehensive, accessible SoC guidelines tailored to sarcoglycanopathies to improve care delivery and readiness for forthcoming disease-modifying therapies.