{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:14Z","timestamp":1787028494356,"version":"build-2736575974"},"reference-count":18,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T00:00:00Z","timestamp":1671235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hereditary transthyretin amyloidosis is the most common form of hereditary amyloidosis, with an autosomal dominant inheritance and a variable penetrance. ATTRv amyloidosis can present as a progressive, axonal sensory autonomic and motor neuropathy or as an infiltrative cardiomyopathy. The definition of biomarkers for the early diagnosis of ATTRv is particularly important in the current era of emerging treatments. In this sense, metabolomics could be an instrument able to provide metabolic profiles with their related metabolic pathways, and we would propose them as possible fluid biomarkers. The aim of this study is to identify altered metabolites (free fatty acids and amino acids) in subjects with a confirmed pathogenic TTR variant. Out of the studied total free fatty acids and amino acids, the serum values of palmitic acid are significantly lower in the ATTRv patients compared to the recruited healthy subjects. The metabolic remodeling identified in this neurogenetic disorder could be the manifestation of pathophysiological processes of the disease, such as mitochondrial dysfunction and neuroinflammation, and contribute to explaining some of its clinical manifestations.<\/jats:p>","DOI":"10.3390\/ijms232416133","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T05:25:46Z","timestamp":1671427546000},"page":"16133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Metabolic Signature of Hereditary Transthyretin Amyloidosis: A Pilot Study"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7539-505X","authenticated-orcid":false,"given":"Marco","family":"Luigetti","sequence":"first","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Guglielmino","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-1509","authenticated-orcid":false,"given":"Angela","family":"Romano","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1490-0320","authenticated-orcid":false,"given":"Maria Ausilia","family":"Sciarrone","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vitali","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Sabino","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3600-392X","authenticated-orcid":false,"given":"Jacopo","family":"Gervasoni","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniello","family":"Primiano","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7448-0604","authenticated-orcid":false,"given":"Lavinia","family":"Santucci","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3477-6136","authenticated-orcid":false,"given":"Rossana","family":"Moroni","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7616-7008","authenticated-orcid":false,"given":"Guido","family":"Primiano","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10941","DOI":"10.1021\/ac402411n","article-title":"Multiplatform Analytical Methodology for Metabolic Fingerprinting of Lung Tissue","volume":"85","author":"Naz","year":"2013","journal-title":"Anal. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"844841","DOI":"10.3389\/fneur.2022.844841","article-title":"Set of Reliable Samples for the Study of Biomarkers for the Early Diagnosis of Parkinson\u2019s Disease","volume":"13","author":"Konjevod","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8848225","DOI":"10.1155\/2020\/8848225","article-title":"A Specific Urinary Amino Acid Profile Characterizes People with Kidney Stones","volume":"2020","author":"Primiano","year":"2020","journal-title":"Dis. Markers"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Calvani, R., Rodriguez-Ma\u00f1as, L., Picca, A., Marini, F., Biancolillo, A., Laosa, O., Pedraza, L., Gervasoni, J., Primiano, A., and Conta, G. (2020). Identification of a Circulating Amino Acid Signature in Frail Older Persons with Type 2 Diabetes Mellitus: Results from the Metabofrail Study. Nutrients, 12.","DOI":"10.3390\/nu12010199"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1080\/13506129.2018.1545640","article-title":"Sudoscan in the evaluation and follow-up of patients and carriers with TTR mutations: Experience from an Italian Centre","volume":"25","author":"Luigetti","year":"2018","journal-title":"Amyloid"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/pst.185","article-title":"Sample size of 12 per group rule of thumb for a pilot study","volume":"4","author":"Julious","year":"2005","journal-title":"Pharm. Stat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1007\/s00415-019-09688-0","article-title":"Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy","volume":"268","author":"Adams","year":"2020","journal-title":"J. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1186\/s13023-020-01633-z","article-title":"Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: A multicenter Italian consensus","volume":"15","author":"Grandis","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1007\/s11357-020-00192-2","article-title":"A novel multi-marker discovery approach identifies new serum biomarkers for Parkinson\u2019s disease in older people: An EXosomes in PArkiNson Disease (EXPAND) ancillary study","volume":"42","author":"Calvani","year":"2020","journal-title":"Geroscience"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1007\/s10072-021-05850-7","article-title":"Neurofilament light chain as a disease severity biomarker in ATTRv: Data from a single-centre experience","volume":"43","author":"Luigetti","year":"2022","journal-title":"Neurol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"902","DOI":"10.3389\/fphys.2017.00902","article-title":"Palmitic Acid: Physiological Role, Metabolism and Nutritional Implications","volume":"8","author":"Carta","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41531-021-00216-4","article-title":"Prognostic biomarkers of Parkinson\u2019s disease in the Spanish EPIC cohort: A multiplatform metabolomics approach","volume":"7","author":"Saiz","year":"2021","journal-title":"NPJ Park. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Havelund, J.F., Heegaard, N.H.H., F\u00e6rgeman, N.J.K., and Gramsbergen, J.B. (2017). Biomarker Research in Parkinson\u2019s Disease Using Metabolite Profiling. Metabolites, 7.","DOI":"10.3390\/metabo7030042"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13024-018-0304-2","article-title":"Recent advances and perspectives of metabolomics-based investigations in Parkinson\u2019s disease","volume":"14","author":"Shao","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1212\/WNL.0000000000003663","article-title":"Metabolomic biomarkers as strong correlates of Parkinson disease progression","volume":"88","author":"LeWitt","year":"2017","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Willkommen, D., Lucio, M., Moritz, F., Forcisi, S., Kanawati, B., Smirnov, K.S., Schroeter, M., Sigaroudi, A., Schmitt-Kopplin, P., and Michalke, B. (2018). Metabolomic investigations in cerebrospinal fluid of Parkinson\u2019s disease. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208752"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e10967","DOI":"10.1097\/MD.0000000000010967","article-title":"Level of uric acid and uric acid\/creatinine ratios in correlation with stage of Parkinson disease","volume":"97","author":"Zhong","year":"2018","journal-title":"Medicine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1152\/physiolgenomics.90407.2008","article-title":"Wfs1 gene deletion causes growth retardation in mice and interferes with the growth hormone pathway","volume":"37","author":"Soomets","year":"2009","journal-title":"Physiol. Genom."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/16133\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:43:27Z","timestamp":1760147007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/16133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,17]]},"references-count":18,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232416133"],"URL":"https:\/\/doi.org\/10.3390\/ijms232416133","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,17]]}}}