Rethinking rare: mitochondrial disease as a model for health system innovation and reform

Abstract

Rare diseases affect over 400 million people worldwide and present a major opportunity for health system reform. Primary mitochondrial disease comprises progressive, genetically heterogeneous disorders caused by pathogenic variants in mitochondrial or nuclear DNA, with an estimated prevalence of 1 in 4300 and likely underdiagnosis due to unequal access to genomic testing. As a complex, multisystem condition requiring coordinated, lifelong care, mitochondrial disease serves as a sentinel for structural challenges in rare disease services, including diagnostic delay, fragmented care and inequitable access to expertise. This study synthesises findings from Project PEARL, integrating a UK-wide survey (n=1000), in-depth interviews with patients and caregivers (n=21), policy analysis and existing evidence on rare disease care to identify system-level implications for healthcare leadership and service design. Four system-level insights emerge. Rare disease services provide a platform to design and test integrated, equity-focused care models. Digital innovation requires transparent and accountable data governance to sustain trust. High-quality care depends on empathy, communication and meaningful patient partnership. Coordinated cross-sector leadership is required to translate innovation into service redesign, workforce development and policy implementation. Mitochondrial disease acts as both an exemplar and a strategic lever for rare disease-driven health system innovation, functioning as a sentinel of system weakness and a testbed for scalable solutions. This approach enables the design, evaluation and scaling of integrated care pathways and ethically governed data infrastructures, providing a practical route to more equitable, coordinated and sustainable healthcare systems.