European Consortium for Lipodystrophies consensus definition and classification framework for monogenic lipodystrophy
Year: 2026
Type: article
Abstract: Lipodystrophy comprises a heterogeneous group of disorders characterized by reduced adipose tissue often associated with severe metabolic complications. Lipodystrophy may be genetic, acquired, or secondary to medical therapies initiated for other conditions. Despite major advances in understanding adipose tissue biology and in human genetic technologies, diagnosis of lipodystrophy is still commonly delayed or missed. Conversely, increasing use of next-generation sequencing has led to proliferation of proposed new genetic causes of lipodystrophy with variable supporting evidence. To address these challenges, an international expert working group from the European Consortium for Lipodystrophies first developed a consensus definition of lipodystrophy as deficient development and/or inadequate maintenance of adipose tissue not attributable to nutritional deprivation or a systemic catabolic state. Anatomical adipose deficiency alone is generally insufficient for diagnosis, with evidence of adipose tissue dysfunction or pathology also usually required. Building on this definition, a framework for evaluating candidate monogenic lipodystrophy syndromes is suggested, based on the strength of human phenotypic, genetic, and biological evidence. Primacy was assigned to direct evidence from affected individuals, with genetic and biological evidence considered supportive but not determinative. This approach accommodates both the variable penetrance and expressivity characteristic of many lipodystrophy syndromes and potential discrepancies between human observations and experimental models. Although the proposed definition is applicable across all forms of lipodystrophy, the classification system described here is restricted to monogenic disorders. Together, these tools aim to improve clinical recognition, promote diagnostic consistency, and provide a robust and adaptable framework for evaluating emerging gene-disease associations in lipodystrophy.
Source: Journal of Internal Medicine
DOI: 10.1111/joim.70157
Authors: Robert K. Semple, Martin Wabitsch, Baris Akinci, Saif Alyaarubi, Marjoleine F. Broekema, Rebecca J. Brown, Giovanni Ceccarini, Carolina Cecchetti, Solaf M. Elsayed, Antía Fernández‐Pombo, Alessandra Gambineri, Ingrid M. Jazet, Lotte Kleinendorst, Konstanze Miehle, Elif A. Oral, Flavia Prodam, Ferruccio Santini, David B. Savage, Nadia Shaukat Ali, Ekaterina Sorkina, Magdalena Szopa, Marie‐Christine Vantyghem, Camille Vatier, Corinne Vigouroux, Julia von Schnurbein, David Araújo‐Vilar
Institutions: Institute of Genetics and Cancer, University of Edinburgh, University Hospital Ulm, Izmir Biomedicine and Genome Center, Amsterdam University Medical Centers, University of Amsterdam, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Azienda Ospedaliera Universitaria Pisana, Ospedale G.B. Morgagni - L.Pierantoni, University of Bologna, Ain Shams University, Universidade de Santiago de Compostela, Center for Research in Molecular Medicine and Chronic Diseases, Instituto de Investigación Sanitaria de Santiago, Leiden University Medical Center, University Hospital Leipzig, Leipzig University, University of Michigan, Michigan Medicine, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, University of Cambridge, Addenbrooke's Hospital, Dubai Health Authority, Newcastle upon Tyne Hospitals NHS Foundation Trust, Jagiellonian University, Inserm, Centre Hospitalier Universitaire de Lille, Recherche translationnelle sur le diabète et les troubles métaboliques, Sorbonne Université, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,780
Funders: U.S. Department of Health and Human Services, Amgen, Eli Lilly and Company, Pfizer, Sanofi, Gilead Sciences, Regeneron Pharmaceuticals, Ionis Pharmaceuticals, Amryt Pharma, European Commission, Fondazione Cariplo, Novo Nordisk, Assistance publique-Hôpitaux de Paris, Xunta de Galicia, Sorbonne Université, National Institutes of Health, Instituto de Salud Carlos III, European Regional Development Fund, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1496055848, G2233490251, G3008857760, G3330753103, G3694284866, G4547686054, Medicina personalizada para las enfermedades raras: diagnóstico por biometría e inteligencia artificial y modificaciones en las marcas epigenéticas en las lipodistrofias infrecuentes., G7903884256, Mechanisms of adipocyte loss in laminopathy-induced lipodystrophy in mice and humans, Tirzepatide for treatment of familial partial lipodystrophy
OpenAlex ID: W7204990653