280th ENMC International Workshop: The ERN EURO-NMD mitochondrial diseases working group; diagnostic criteria and outcome measures in primary mitochondrial myopathies. Hoofddorp, the Netherlands, 22-24 November 2024

Michelangelo Mancuso; Piervito Lopriore; Luisa Semmler; Cornelia Kornblum; 280th ENMC workshop study group

doi:10.1016/j.nmd.2025.105340

280th ENMC International Workshop: The ERN EURO-NMD mitochondrial diseases working group; diagnostic criteria and outcome measures in primary mitochondrial myopathies. Hoofddorp, the Netherlands, 22-24 November 2024

Neuromuscul Disord. 2025 May:50:105340. doi: 10.1016/j.nmd.2025.105340. Epub 2025 Mar 22.

Authors

Michelangelo Mancuso¹, Piervito Lopriore², Luisa Semmler³, Cornelia Kornblum⁴; 280th ENMC workshop study group

Collaborators

280th ENMC workshop study group:
Rafael Artuch⁵, Marcello Bellusci⁶, Enrico Bertini⁷, Valerio Carelli⁸, Felix Distelmaier⁹, Michio Hirano¹⁰, Rita Horvath¹¹, Mirian Ch Janssen¹², Amel Karaa¹³, Thomas Klopstock¹⁴, Cornelia Kornblum¹⁵, Costanza Lamperti¹⁶, Piervito Lopriore¹⁷, Robert McFarland¹⁸, Yi Shiau Ng¹⁸, Michelangelo Mancuso¹⁷, Holger Prokisch¹⁹, Shamima Rahman²⁰, Manuel Schiff²¹, Luisa Semmler³, Servidei Serenella²², Tanja Taivassalo²³, John Vissing²⁴, Jelle van den Ameele¹¹, Katie Waller²⁵

Affiliations

¹ Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy. Electronic address: michelangelo.mancuso@unipi.it.
² Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy; PhD School in Translational Medicine, Scuola Superiore Sant'Anna, Pisa, Italy.
³ Department of Neurology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
⁴ Department of Neuromuscular Diseases, Center for Neurology, University Hospital Bonn, Germany.
⁵ Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III and Hospital Sant Joan de Déu, Barcelona, Spain.
⁶ Reference Center for Inherited Metabolic Disorders MetabERN, Mitochondrial Disorders Research Group (imas12), '12 de Octubre' University Hospital, Madrid, Spain.
⁷ Bambino Gesù Hospital IRCCS, Rome, Italy.
⁸ IRCCS Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital and Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; Patrick Chinnery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
⁹ University Children's Hospital, Düsseldorf, Germany.
¹⁰ Columbia University Irving Medical Center, New York, USA.
¹¹ Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
¹² Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
¹³ Mass General Hospital/Harvard Medical School, Boston USA.
¹⁴ Department of Neurology, Friedrich-Baur-Institute, LMU University Hospital, Ludwig-Maximilians-Universität München, Munich; German Center for Neurodegenerative Diseases (DZNE); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
¹⁵ Department of Neuromuscular Diseases, Center for NeurologyUniversity Hospital Bonn, Bonn, Germany.
¹⁶ Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
¹⁷ University of Pisa, Italy.
¹⁸ Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK; NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
¹⁹ School of Medicine, Technical University of Munich, Munich, Germany; German Center for Child and Adolescent Health (DZKJ), partner site Munich, Munich, Germany; Institute of Neurogenomics, Computational Health Centre, Helmholtz Zentrum München, Neuherberg, Germany.
²⁰ UCL Great Ormond Street Institute of Child Health, London, UK.
²¹ Reference Center for Mitochondrial Disorders (CARAMMEL) and Reference Center for Inborn Errors of Metabolism, Department of Pediatrics, Necker-Enfants-Malades Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris-Cité, MetabERN, Paris; 22INSERM UMRS_1163, Imagine Institute, Paris, France.
²² Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Dipartimento Di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy.
²³ Department of Physiology and Aging, Clinical Translational Research Building, University of Florida, 2004 Mowry Road, Gainesville, FL, USA.
²⁴ Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
²⁵ Lily Foundation, UK.

PMID: 40273815
DOI: 10.1016/j.nmd.2025.105340

Abstract

The 280th ENMC International Workshop, held in Hoofddorp, The Netherlands, November 22-24, 2024, focused on primary mitochondrial myopathies (PMM). The workshop aimed to update diagnostic criteria, outcome measures, and explore new digital health technologies (DHTs) in the context of clinical trial design and conduct for PMM. Key points discussed included: (i) PMM definition and phenotypes; PMM are genetically determined mitochondrial disorders with prominent skeletal muscle involvement with two major phenotypes: mitochondrial myopathy (MiMy) either with or without chronic progressive external ophthalmoplegia (PEO); (ii) diagnostic criteria, with emphasis on the importance of genetic testing and muscle biopsy for accurate diagnosis; (iii) outcome measures: consensus on clinical scales, functional tests, performance measures, and patient-reported outcome measures (PROMs) for both adults and children; (iv) digital health technologies, with exploration of wearable and non-wearable technologies for gait analysis, physical activity monitoring, and other assessments; (v) potential and limitations of biomarkers for PMM diagnosis and monitoring. The workshop concluded with a strong consensus on the updated definition of PMM, its phenotypes, and the recommended outcome measures for clinical studies. Further research is needed to validate digital health technologies and biomarkers for PMM.

Keywords: Biomarkers; Clinical trials; Diagnostic criteria; Outcome measures; Primary mitochondrial myopathy.

MeSH terms

Humans
Mitochondrial Myopathies* / diagnosis
Mitochondrial Myopathies* / genetics
Mitochondrial Myopathies* / therapy
Netherlands
Outcome Assessment, Health Care*
Patient Reported Outcome Measures