{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:27:29Z","timestamp":1760146049306,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Leigh syndrome spectrum (LSS) is a novel nomenclature that encompasses both classical Leigh syndrome and Leigh-like phenotypes. Given the heterogeneity of disease presentation, a new consensus published recently addressed the main issues and proposed general guidelines towards diagnosis. Based on these recommendations, we developed a simple pipeline that can be useful in the diagnosis of LSS. Methods: We combined previously published criteria with our own experience to achieve a diagnostic framework that can provide faster satisfactory results with fewer resources. Results: We suggest adding basic biochemical tests for amino acids, acylcarnitine, and urinary organic acids as parallel investigations, as these results can be obtained in a short time. This approach characterized 80% of our cohort and promoted specific intervention in 10% of confirmed cases. Conclusions: Genetic studies are crucial in the diagnosis of LSS, but they are time-consuming and might delay tailored interventions. Therefore, we suggest adding more affordable and less complex biochemical studies as primary tests when investigating treatable causes of LSS.<\/jats:p>","DOI":"10.3390\/diagnostics14192133","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T04:05:46Z","timestamp":1727323546000},"page":"2133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Comprehensive Approach to the Diagnosis of Leigh Syndrome Spectrum"],"prefix":"10.3390","volume":"14","author":[{"given":"Manuela Schubert","family":"Baldo","sequence":"first","affiliation":[{"name":"Research and Development Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, 4000-053 Porto, Portugal"},{"name":"School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Lu\u00edsa","family":"Azevedo","sequence":"additional","affiliation":[{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-346 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-600 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6471-4067","authenticated-orcid":false,"given":"Margarida Paiva","family":"Coelho","sequence":"additional","affiliation":[{"name":"School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-346 Porto, Portugal"},{"name":"Pediatrics Department, Northern Mother and Child Centre, Reference Centre for Metabolic Disorders, Santo Ant\u00f3nio Hospital University Centre, 4050-651 Porto, Portugal"}]},{"given":"Esmeralda","family":"Martins","sequence":"additional","affiliation":[{"name":"School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-346 Porto, Portugal"},{"name":"Pediatrics Department, Northern Mother and Child Centre, Reference Centre for Metabolic Disorders, Santo Ant\u00f3nio Hospital University Centre, 4050-651 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6186-779X","authenticated-orcid":false,"given":"Laura","family":"Vilarinho","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, 4000-053 Porto, Portugal"},{"name":"Neonatal Screening, Metabolism and Genetics Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, 4000-053 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1136\/jnnp-2012-304426","article-title":"A guide to diagnosis and treatment of Leigh syndrome","volume":"85","author":"Baertling","year":"2014","journal-title":"J. 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