Adenylosuccinate synthase 1 (ADSS1) myopathy is an ultra-rare autosomal recessive disorder of purine metabolism characterized by progressive muscle weakness, respiratory insufficiency and variable cardiac involvement. The 2nd Clinical and Scientific Conference on ADSS1 Myopathy, held at Boston Children’s Hospital on 24 October 2025, brought together clinicians, researchers, patient advocates and therapeutic development partners to review advances in disease biology, clinical care and treatment development. Clinical presentations highlighted an expanding phenotype encompassing mitochondrial abnormalities, neuromuscular junction dysfunction and disturbed muscle energy metabolism. Quantitative muscle imaging, electrical impedance myography, phosphorus magnetic resonance spectroscopy and circulating molecular signatures emerged as candidate measures for disease monitoring and therapeutic evaluation. Following US regulatory clearance, the first Phase 1b trial of adenylosuccinic acid was presented, marking progression toward clinical translation. Complementary yeast, nematode, human cell and mouse models provided insights into disrupted nucleotide homeostasis and downstream cellular dysfunction, while preclinical gene replacement studies demonstrated functional and metabolic rescue. Discussions identified priorities for harmonized natural history studies, biomarker validation, individualized respiratory and exercise guidance, and coordinated evaluation of metabolic, genetic and repurposed therapies. This report summarizes the meeting’s findings and priorities for integrating mechanistic research with international clinical infrastructure to advance patient care and therapeutic development.
