{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:04:09Z","timestamp":1771923849943,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006400","name":"Alnylam Pharmaceuticals","doi-asserted-by":"publisher","award":["BR-AHP-21-286"],"award-info":[{"award-number":["BR-AHP-21-286"]}],"id":[{"id":"10.13039\/100006400","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Acute hepatic porphyrias (AHP) represent a rare group of inherited metabolic disorders of heme biosynthesis pathway. This study aims to determine the diagnostic and prognostic value of serum neurofilament light chain (NfL) as potential biomarker for AHP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a cross-sectional observational study to evaluate NfL levels in patients with AHP. They were divided in different groups: normal health individuals; patients with definitive diagnosis of AHP during acute episodes; patients with AHP and infrequent attacks; patients with AHP and recurrent attacks; asymptomatic individuals with positive genetic testing and urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels elevated 4 or more times (\u201chigh excretors\u201d); asymptomatic individuals with exclusive positive genetic test; control group with Hereditary Amyloidosis related to Transthyretin with Polyneuropathy (ATTRv-PN).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During acute attacks, serum NfL levels were 68 times higher compared to normal controls and disclosed a strong correlation with ALA and PBG levels; also exhibited elevated levels in patients with chronic symptoms regardless of the number of disease attacks compared to healthy controls, and at similar levels to patients with ATTRv-PN, which is a model of progressive neuropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study represents the first to establish NfL as a biomarker for AHP, disclosing NfL as a sensitive biomarker for axonal damage and chronic symptom occurrence. This study not only underscores that neurological damage associated with the disease in any patient, irrespective of the number of attacks, but also reinforces the progressive and profoundly debilitating nature of acute and chronic symptoms observed in individuals with AHP.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1384678","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T14:06:57Z","timestamp":1713449217000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Neurofilament light chain as a biomarker for acute hepatic porphyrias"],"prefix":"10.3389","volume":"15","author":[{"given":"Paulo","family":"Sgobbi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo de Lima","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno de Mattos Lombardi","family":"Badia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor Braga","family":"Farias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9lvia Bertoldo de","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alana Strucker","family":"Barbosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila Alves","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa de Freitas","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00cdcaro Fran\u00e7a Navarro","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Acary Souza Bulle","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wladimir Bocca Vieira de Rezende","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1590\/0004-282X20200096","article-title":"Acute hepatic porphyrias for the neurologist: current concepts and perspectives","volume":"79","author":"Souza","year":"2021","journal-title":"Arq Neuropsiquiatr"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1053\/j.gastro.2022.11.034","article-title":"AGA clinical practice updated on diagnosis and management of acute hepatic porphyrias: expert review","volume":"164","author":"Wang","year":"2023","journal-title":"Gastroenterology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"715523","DOI":"10.3389\/fnins.2021.715523","article-title":"Acute hepatic porphyria: pathophysiological basis of neuromuscular manifestations","volume":"15","author":"Souza","year":"2021","journal-title":"Front Neurosci"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e2389","DOI":"10.1002\/brb3.2389","article-title":"Acute porphyrias\u2014a neurological perspective","volume":"11","author":"Gerischer","year":"2021","journal-title":"Brain Behav"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.ymgme.2019.10.011","article-title":"Porphyria-induced posterior reversible encephalopathy syndrome and central nervous system dysfunction","volume":"128","author":"Jaramillo-Calle","year":"2019","journal-title":"Mol Genet Metab"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1002\/hep.29313","article-title":"Acute hepatic porphyrias: recommendations for evaluation and long-term management","volume":"66","author":"Balwani","year":"2017","journal-title":"Hepatology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"4330","DOI":"10.1007\/s12325-022-02172-8","article-title":"Patient perspective on acute hepatic porphyria with sporadic attacks: a chronic disease with substantial health-related quality of life impacts","volume":"39","author":"Wheeden","year":"2022","journal-title":"Adv Ther"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1002\/hep.30936","article-title":"EXPLORE: a prospective, multinational, natural history study of patients with acute hepatic porphyria with recurrent attacks","volume":"71","author":"Gouya","year":"2020","journal-title":"Hepatology"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s13023-023-02653-1","article-title":"Brazilian registry of patients with porphyria: REBRAPPO study","volume":"18","author":"Souza","year":"2023","journal-title":"Orphanet J Rare Dis"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.ceb.2020.10.011","article-title":"The dazzling rise of neurofilaments: physiological functions and roles as biomarkers","volume":"68","author":"Bomont","year":"2021","journal-title":"Curr Opin Cell Biol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1093\/brain\/awac328","article-title":"The multifaceted role of neurofilament light chain protein in non-primary neurological diseases","volume":"146","author":"Abu-Rumeileh","year":"2023","journal-title":"Brain"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/s13054-023-04497-4","article-title":"Neurofilament light chain to assess sepsis-associated encephalopathy: are we on the track toward clinical implementation?","volume":"27","author":"Bircak-Kuchtova","year":"2023","journal-title":"Crit Care"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1097\/YCO.0000000000000756","article-title":"Neurofilament light protein as a biomarker in depression and cognitive function","volume":"35","author":"Travica","year":"2022","journal-title":"Curr Opin Psychiatry"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1161\/HYPERTENSIONAHA.117.10314","article-title":"Neurofilament as neuronal injury blood marker in preeclampsia","volume":"71","author":"Evers","year":"2018","journal-title":"Hypertension"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/s41582-019-0210-4","article-title":"Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease","volume":"15","author":"Adams","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.jad.2008.06.026","article-title":"The PHQ-8 as a measure of current depression in the general population","volume":"114","author":"Kroenke","year":"2009","journal-title":"J Affect Disord"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1002\/jmd2.12343","article-title":"Quantifying the impact of symptomatic acute hepatic porphyria on well-being via patient-reported outcomes: results from the Porphyria worldwide patient experience research (POWER) study","volume":"64","author":"Dickey","year":"2022","journal-title":"JIMD Rep"},{"key":"ref18","volume-title":"User\u2019s manual for the SF-12v2 health survey","author":"Maruish","year":"2012"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12955-020-01328-w","article-title":"Health-related quality of life in porphyria cutanea tarda: a cross-sectional registry based study","volume":"18","author":"Andersen","year":"2020","journal-title":"Health Qual Life Outcomes"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","article-title":"Neurofilaments as biomarkers in neurological disorders","volume":"14","author":"Khalil","year":"2018","journal-title":"Nat Rev Neurol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1002\/jimd.12551","article-title":"EXPLORE B: a prospective, long-term natural history study of patients with acute hepatic porphyria with chronic symptoms","volume":"45","author":"Cassiman","year":"2022","journal-title":"J Inherit Metab Dis"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2289","DOI":"10.1056\/NEJMoa1913147","article-title":"Phase 3 trial of RNAi therapeutic givosiran for acute intermittent porphyria","volume":"382","author":"Balwani","year":"2020","journal-title":"N Engl J Med"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/liv.15090","article-title":"Efficacy and safety of givosiran for acute hepatic porphyria: 24-month interim analysis of the randomized phase 3 ENVISION study","volume":"42","author":"Ventura","year":"2022","journal-title":"Liver Int"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1016\/j.jhep.2023.06.013","article-title":"Efficacy and safety of givosiran for acute hepatic porphyria: final results of the randomized phase III ENVISION trial","volume":"79","author":"Kuter","year":"2023","journal-title":"J Hepatol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s13023-021-01742-3","article-title":"Health impact of acute intermittent porphyria in latent and non-recurrent attacks patients","volume":"16","author":"Buend\u00eda-Mart\u00ednez","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1186\/s13023-023-02913-0","article-title":"Clinical features of acute attacks, chronic symptoms, and long-term complications among patients with acute hepatic porphyria in Japan: a real-world claims database study","volume":"18","author":"Horie","year":"2023","journal-title":"Orphanet J Rare Dis"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1007\/s10545-018-0178-z","article-title":"Medical and financial burden of acute intermittent porphyria","volume":"41","author":"Neeleman","year":"2018","journal-title":"J Inherit Metab Dis"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1080\/00207454.2019.1655014","article-title":"Neurological and neuropsychiatric manifestations of porphyria","volume":"129","author":"Suh","year":"2019","journal-title":"Int J Neurosci"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1007\/s11910-022-01205-7","article-title":"Neurological manifestations of acute porphyrias","volume":"22","author":"Wylie","year":"2022","journal-title":"Curr Neurol Neurosci Rep"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1212\/WNL.0000000000200752","article-title":"NfL as analogue of C-reactive protein in neurologic diseases: instructions for use","volume":"98","author":"Gaetani","year":"2022","journal-title":"Neurology"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1002\/acn3.51234","article-title":"Blood neurofilament light: a critical review of its application to neurologic disease","volume":"7","author":"Barro","year":"2020","journal-title":"Ann Clin Transl Neurol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1111\/ene.15813","article-title":"Serum neurofilament light chain cut-off definition for clinical diagnosis and prognosis of amyotrophic lateral sclerosis","volume":"30","author":"Brousse","year":"2023","journal-title":"Eur J Neurol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1093\/brain\/awad267","article-title":"The potential of blood neurofilament light as a marker for neurodegeneration for Alzheimer\u2019s disease","volume":"147","author":"Jung","year":"2024","journal-title":"Brain"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2954","DOI":"10.1093\/brain\/awab241","article-title":"The potential of serum neurofilament as biomarker for multiple sclerosis","volume":"144","author":"Bittner","year":"2021","journal-title":"Brain"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"959261","DOI":"10.3389\/fnins.2022.959261","article-title":"Neurofilament light as a biomarker for motor decline in Parkinson\u2019s disease","volume":"16","author":"Liu","year":"2022","journal-title":"Front Neurosci"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1002\/acn3.51207","article-title":"Ratio and index of neurofilament light chain indicate its origins in Guillain\u2013Barr\u00e9 syndrome","volume":"7","author":"K\u00f6rtvelyessy","year":"2020","journal-title":"Ann Clin Transl Neurol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.parkreldis.2018.06.018","article-title":"Serum neurofilament light chain in progressive suparanuclear palsy","volume":"56","author":"Donker Kaat","year":"2018","journal-title":"Parkinsonism Relat Disord"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1002\/acn3.678","article-title":"Serum Neurofilament light correlates with CADASIL disease severity and survival","volume":"6","author":"Gravesteijn","year":"2018","journal-title":"Ann Clin Transl Neurol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1038\/s41467-021-22114-2","article-title":"Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy","volume":"12","author":"Weinhofer","year":"2021","journal-title":"Nat Commun"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"e412","DOI":"10.1212\/WNL.0000000000011090","article-title":"Neurofilament light chain as a biomarker of hereditary transthyretin-mediated amyloidosis","volume":"96","author":"Ticau","year":"2021","journal-title":"Neurology"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1384678\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T11:41:35Z","timestamp":1713872495000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1384678\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,18]]},"references-count":40,"alternative-id":["10.3389\/fneur.2024.1384678"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2024.1384678","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,18]]},"article-number":"1384678"}}