A National Biobank Framework for Rare Diseases: Standardized Infrastructure and Cross-Institutional Collaboration Accelerating Translational Innovation in China

Rare diseases (RDs) collectively affect >400 million people worldwide, but fragmented infrastructure and biospecimen scarcity impede progress. China's heterogeneous healthcare landscape magnifies these challenges. Since 2016, the ISO 20387:2018-accredited Peking Union Medical College Hospital (PUMCH) RD Biobank has pioneered a scalable model integrating 446 institutions via national networks. Our secure digital platform standardizes biospecimen protocols (acquisition/processing/storage) and enables ethical data/specimen sharing through auditable MTAs/DUAs. Among 49,759 enrolled patients, 73.13% were diagnosed, while 26.87% were undiagnosed, with pediatric cases (50.75%) and males (52.39%) predominating. Phenotypic analysis showed 78.51% single-system versus 21.20% multisystem involvement. Top diagnoses included congenital scoliosis and progressive muscular dystrophy. Specimen diversity revealed system-specific patterns: musculoskeletal/nervous/sensory systems linked to multiple specimen types; immune/genitourinary to fluids; cardiovascular/neoplastic to derivatives; endocrine uniquely to tissues. Nucleic acids (93.4%) and blood specimens (21.4%) formed core resources, while iPSCs/organoids prioritized for cardiovascular/neoplastic RDs enable functional validation. This framework transcends biospecimen fragmentation by uniting clinical, molecular, and institutional dimensions. It demonstrates how centralized governance and interoperable systems can accelerate RD research globally. By transforming isolated data into collaborative discovery engines, we provide a blueprint for converting RD challenges into precision diagnostics and therapies, which are urgently needed for the millions of individuals worldwide who remain undiagnosed.