{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:50:11Z","timestamp":1791366611140,"version":"4.3.1"},"reference-count":18,"publisher":"Georg Thieme Verlag KG","issue":"08","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arq Neuropsiquiatr"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Rhabdomyolysis is a potentially life-threatening condition that can result from genetic causes. Despite that, little is known about the genetic underpinnings behind monogenic rhabdomyolysis in Brazil.<\/jats:p>\n                  <jats:p>To address the frequency and predictive factors for monogenic causes of rhabdomyolysis in a Brazilian series.<\/jats:p>\n                  <jats:p>Patients presenting with rhabdomyolysis at Universidade Estadual de Campinas (UNICAMP) from April 2024 to October 2025 were selected. Rhabdomyolysis was defined when (1) there was at least 1 episode of creatine kinase (CK) levels \u2265 5x upper limit of normal (ULN) not better explained by exogeneous factors and (2) at least 1 of the RHABDO criteria (R - recurrent episodes of exertional rhabdomyolysis; H - hyperCKemia persisting more than 8 weeks after event; A: accustomed physical exercise; B - blood creatine kinase (CK)\u2009&gt;\u200950x ULN; D \u2013 drug ingestion\/medication\/supplements or other exogenous and endogenous factors cannot sufficiently explain the rhabdomyolysis severity; O - other family members affected \/ other exertional symptoms [e.g., cramps or myalgia]). was met. A 2-step genetic investigation was undertaken: first a 50-gene panel enriched in metabolic myopathy genes and for those with negative results, whole exome sequencing (WES). Clinical and demographic data of patients with and without gene etiology were then compared.<\/jats:p>\n                  <jats:p>We identified 20 patients, 8 of whom were men, with mean age at the first episode of rhabdomyolysis of 19.5 (2\u201350) years old. Monogenic etiology was found in 9 of the patients. The associated genes were PYGM (most frequent), CPT II, ACADS, ACADM, ANO5, DYSF and FKTN. Creatine kinase \u2265 5x ULN persisting for more than 8 weeks after the event (p\u2009=\u20090.0081), myalgia (p 0.028), objective weakness (p\u2009=\u20090.049) and parental consanguinity (p\u2009=\u20090.0090) were more frequent in the group with genetic cause.<\/jats:p>\n                  <jats:p>After properly exclusion of exogenous etiologies, monogenic causes accounted for nearly half of the cases of rhabdomyolysis. Genetic testing should be pursued in those patients with persistent CK elevation, presence of myalgia, objective weakness or parental consanguinity.<\/jats:p>","DOI":"10.1055\/s-0046-1827166","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T23:19:04Z","timestamp":1786663144000},"page":"001-007","source":"Crossref","is-referenced-by-count":0,"title":["When to think of genetic causes for rhabdomyolysis? A Brazilian single-center exploratory study"],"prefix":"10.1055","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1780-9600","authenticated-orcid":false,"given":"Aldrin Pedroza","family":"Martins","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas, Faculdade de Ci\u00eancias M\u00e9dicas, Departamento de Neurologia, Campinas SP, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7160-0853","authenticated-orcid":false,"given":"Alberto Rolim Muro","family":"Martinez","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas, Faculdade de Ci\u00eancias M\u00e9dicas, Departamento de Neurologia, Campinas SP, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1371-1579","authenticated-orcid":false,"given":"Anamarli","family":"Nucci","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas, Faculdade de Ci\u00eancias M\u00e9dicas, Departamento de Neurologia, Campinas SP, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0898-2419","authenticated-orcid":false,"given":"Marcondes Cavalcante","family":"Fran\u00e7a J\u00fanior","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas, Faculdade de Ci\u00eancias M\u00e9dicas, Departamento de Neurologia, Campinas SP, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.ejim.2006.09.020","article-title":"The syndrome of rhabdomyolysis: Pathophysiology and diagnosis","volume":"18","author":"G D Giannoglou","year":"2007","journal-title":"Eur J Intern Med"},{"issue":"07","key":"ref2","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.nmd.2021.04.007","article-title":"Risk factors and future directions for preventing and diagnosing exertional rhabdomyolysis","volume":"31","author":"A Carneiro","year":"2021","journal-title":"Neuromuscul Disord"},{"issue":"06","key":"ref3","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.medcli.2011.05.021","article-title":"[Rhabdomyolysis. A descriptive study of 449 patients]","volume":"139","author":"J H Garc\u00eda","year":"2012","journal-title":"Med Clin (Barc)"},{"issue":"06","key":"ref4","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1097\/01.md.0000188565.48918.41","article-title":"Rhabdomyolysis: an evaluation of 475 hospitalized patients","volume":"84","author":"G Melli","year":"2005","journal-title":"Medicine (Baltimore)"},{"issue":"04","key":"ref5","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1007\/s00415-019-09185-4","article-title":"A systematic review on the definition of rhabdomyolysis","volume":"267","author":"K Stahl","year":"2020","journal-title":"J Neurol"},{"issue":"06","key":"ref6","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1002\/mus.24606","article-title":"Diagnostic evaluation of rhabdomyolysis","volume":"51","author":"J R Nance","year":"2015","journal-title":"Muscle Nerve"},{"issue":"02","key":"ref7","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1111\/ene.14553","article-title":"The etiology of rhabdomyolysis: an interaction between genetic susceptibility and external triggers","volume":"28","author":"N Kruijt","year":"2021","journal-title":"Eur J Neurol"},{"issue":"10","key":"ref8","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1111\/j.1469-8749.2012.04320.x","article-title":"Myopathic causes of exercise intolerance with rhabdomyolysis","volume":"54","author":"R Quinlivan","year":"2012","journal-title":"Dev Med Child Neurol"},{"issue":"01","key":"ref9","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13023-015-0264-3","article-title":"Rhabdomyolysis: a genetic perspective","volume":"10","author":"R S Scalco","year":"2015","journal-title":"Orphanet J Rare Dis"},{"issue":"05","key":"ref10","doi-asserted-by":"publisher","first-page":"954","DOI":"10.3390\/genes14050954","article-title":"Metabolic Myopathies in the Era of Next-Generation Sequencing","volume":"14","author":"J A Urtizberea","year":"2023","journal-title":"Genes (Basel)"},{"issue":"01","key":"ref11","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1136\/practneurol-2018-002008","article-title":"How to do it: investigate exertional rhabdomyolysis (or not)","volume":"19","author":"P M Fernandes","year":"2019","journal-title":"Pract Neurol"},{"issue":"09","key":"ref12","doi-asserted-by":"publisher","first-page":"995","DOI":"10.3390\/genes16090995","article-title":"Rhabdomyolysis in the Era of Next-Generation Sequencing: Selecting Patients with a High Likelihood of a Genetic Susceptibility Using \u2018RHABDO\u2019 Features","volume":"16","author":"N Kruijt","year":"2025","journal-title":"Genes (Basel)"},{"issue":"07","key":"ref13","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.3390\/genes14071393","article-title":"NGS-Based Genetic Analysis in a Cohort of Italian Patients with Suspected Inherited Myopathies and\/or HyperCKemia","volume":"14","author":"F Invernizzi","year":"2023","journal-title":"Genes (Basel)"},{"issue":"05","key":"ref14","doi-asserted-by":"publisher","first-page":"e352","DOI":"10.1212\/NXG.0000000000000352","article-title":"Next-generation sequencing approach to hyperCKemia: A 2-year cohort study","volume":"5","author":"A Rubegni","year":"2019","journal-title":"Neurol Genet"},{"issue":"03","key":"ref15","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1097\/CND.0b013e31822721ca","article-title":"Exertional rhabdomyolysis: a clinical review with a focus on genetic influences","volume":"13","author":"M E Landau","year":"2012","journal-title":"J Clin Neuromuscul Dis"},{"issue":"01","key":"ref16","doi-asserted-by":"publisher","first-page":"e000151","DOI":"10.1136\/bmjsem-2016-000151","article-title":"Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?","volume":"2","author":"R S Scalco","year":"2016","journal-title":"BMJ Open Sport Exerc Med"},{"issue":"03","key":"ref17","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1017\/cjn.2017.286","article-title":"Next-Generation Sequencing to Diagnose Muscular Dystrophy, Rhabdomyolysis, and HyperCKemia","volume":"45","author":"L Wu","year":"2018","journal-title":"Can J Neurol Sci"},{"issue":"7809","key":"ref20","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"K J Karczewski","year":"2020","journal-title":"Nature"}],"container-title":["Arquivos de Neuro-Psiquiatria"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0046-1827166.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:56:41Z","timestamp":1791363401000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0046-1827166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":18,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2026,5,12]]},"published-print":{"date-parts":[[2026,8]]}},"alternative-id":["s00461827166"],"URL":"https:\/\/doi.org\/10.1055\/s-0046-1827166","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0004-282X","1678-4227"],"issn-type":[{"value":"0004-282X","type":"print"},{"value":"1678-4227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]}}}