{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:26:18Z","timestamp":1792009578345,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005941","name":"Dietmar Hopp Stiftung","doi-asserted-by":"publisher","award":["23011221"],"award-info":[{"award-number":["23011221"]}],"id":[{"id":"10.13039\/501100005941","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005941","name":"Dietmar Hopp Stiftung","doi-asserted-by":"publisher","award":["DH2011117"],"award-info":[{"award-number":["DH2011117"]}],"id":[{"id":"10.13039\/501100005941","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aims to elucidate the long\u2010term benefit of newborn screening (NBS) for individuals with long\u2010chain 3\u2010hydroxy\u2010acyl\u2010CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiency, inherited metabolic diseases included in NBS programs worldwide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>German national multicenter study of individuals with confirmed LCHAD\/MTP deficiency identified by NBS between 1999 and 2020 or selective metabolic screening. Analyses focused on NBS results, confirmatory diagnostics, and long\u2010term clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty\u2010seven individuals with LCHAD\/MTP deficiency were included in the study, thereof 54 identified by NBS. All screened individuals with LCHAD deficiency survived, but four with MTP deficiency (14.8%) died during the study period. Despite NBS and early treatment neonatal decompensations (28%), symptomatic disease course (94%), later metabolic decompensations (80%), cardiomyopathy (28%), myopathy (82%), hepatopathy (32%), retinopathy (17%), and\/or neuropathy (22%) occurred. Hospitalization rates were high (up to a mean of 2.4 times\/year). Disease courses in screened individuals with LCHAD and MTP deficiency were similar except for neuropathy, occurring earlier in individuals with MTP deficiency (median 3.9 vs. 11.4\u2009years; <jats:italic>p<\/jats:italic>\u2009=\u20090.0447). Achievement of dietary goals decreased with age, from 75% in the first year of life to 12% at age 10, and consensus group recommendations on dietary management were often not achieved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>While NBS and early treatment result in improved (neonatal) survival, they cannot reliably prevent long\u2010term morbidity in screened individuals with LCHAD\/MTP deficiency, highlighting the urgent need of better therapeutic strategies and the development of disease course\u2010altering treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52002","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T07:13:33Z","timestamp":1706080413000},"page":"883-898","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neurological outcome in long\u2010chain hydroxy fatty acid oxidation disorders"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4251-7257","authenticated-orcid":false,"given":"Ulrike","family":"M\u00fctze","sequence":"first","affiliation":[{"name":"Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Ottenberger","sequence":"additional","affiliation":[{"name":"Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gleich","sequence":"additional","affiliation":[{"name":"Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther M.","family":"Maier","sequence":"additional","affiliation":[{"name":"Dr. von Hauner Children's Hospital, Ludwig\u2010Maximilians\u2010University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lindner","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology University Children's Hospital Frankfurt  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf A.","family":"Husain","sequence":"additional","affiliation":[{"name":"Center for Inborn Metabolic Disorders, Department of Neuropediatrics Jena University Hospital  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Palm","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetology and Metabolic Medicine University Children's Hospital  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skadi","family":"Beblo","sequence":"additional","affiliation":[{"name":"Department of Women and Child Health, Hospital for Children and Adolescents, Center for Pediatric Research Leipzig (CPL) University Hospitals, University of Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Freisinger","sequence":"additional","affiliation":[{"name":"Children's Hospital Reutlingen, Klinikum am Steinenberg  Reutlingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Santer","sequence":"additional","affiliation":[{"name":"University Medical Center Hamburg\u2010Eppendorf, University Children's Hospital  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Thimm","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology, and Pediatric Cardiology University Children's Hospital, Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"vom Dahl","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases University Hospital, Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Weinhold","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Center of Chronically Sick Children Charit\u00e9 \u2010 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Grohmann\u2010Held","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine University Medicine Greifswald  Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Haase","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Helios Hospital Erfurt  Erfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia B.","family":"Hennermann","sequence":"additional","affiliation":[{"name":"Villa Metabolica, Center for Pediatric and Adolescent Medicine Mainz University Medical Center  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"H\u00f6rbe\u2010Blindt","sequence":"additional","affiliation":[{"name":"Prof.\u2010Hess Children's Hospital Clinic Bremen Mitte  Bremen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Kamrath","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics and Neonatology University Hospital of Gie\u00dfen and Marburg  Gie\u00dfen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Marquardt","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Children's Hospital Oldenburg  Oldenburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Marquardt","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Metabolic Diseases University Children's Hospital Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Behne","sequence":"additional","affiliation":[{"name":"Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothea","family":"Haas","sequence":"additional","affiliation":[{"name":"Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Spiekerkoetter","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology Medical Center \u2010 University of Freiburg, Faculty of Medicine  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg F.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven F.","family":"Garbade","sequence":"additional","affiliation":[{"name":"Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5986-0468","authenticated-orcid":false,"given":"Sarah C.","family":"Gr\u00fcnert","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology Medical Center \u2010 University of Freiburg, Faculty of Medicine  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"K\u00f6lker","sequence":"additional","affiliation":[{"name":"Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1302"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010physiol\u2010021115\u2010105045"},{"key":"e_1_2_9_4_1","unstructured":"NCBI GenBank.Homo sapiens hydroxyacyl\u2010CoA dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA) mRNA; nuclear gene for mitochondrial product. Accessed March 16 2022.https:\/\/www.ncbi.nlm.nih.gov\/nuccore\/NM_000182.5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010010\u20109090\u2010x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12372"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2016.06.007"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571\u2010020\u201000955\u20107"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2015.03.002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010012\u20109484\u2010z"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010012\u20109483\u20100"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2020-0444"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20106\u201044"},{"key":"e_1_2_9_14_1","unstructured":"Gemeinsamer Bundesausschuss.Beschlusstext: Kinder\u2010Richtlinien (Neufassung Anlage 2: Neugeborenen\u2010Screening und weitere Themen). Accessed November 14 2022.https:\/\/www.g\u2010ba.de\/beschluesse\/170\/"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.109.1.99"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20103476(97)70312\u20103"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10211"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010009\u20101125\u20109"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010015\u20100236\u20107"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2016_558"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13092925"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2022.100884"},{"key":"e_1_2_9_23_1","unstructured":"AWMF.Konfirmationsdiagnostik bei Verdacht auf angeborene Stoffwechselkrankheiten aus dem Neugeborenenscreening 027\u2010021. AWMF. Accessed June 15 2020.https:\/\/www.awmf.org\/leitlinien\/detail\/ll\/027\u2010021.html"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0887\u20108994(96)00021\u20105"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1043"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12279"},{"key":"e_1_2_9_27_1","unstructured":"Statistisches Bundesamt.Eckdaten der Krankenhauspatientinnen und \u2010patienten. Accessed November 14 2022.https:\/\/www.destatis.de\/DE\/Themen\/Gesellschaft\u2010Umwelt\/Gesundheit\/Krankenhaeuser\/Tabellen\/entlassene\u2010patienten\u2010eckdaten.html"},{"key":"e_1_2_9_28_1","unstructured":"NCBI GenBank.Homo sapiens hydroxyacyl\u2010CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB) transcript variant 1 mRNA; nuclear gene for mitochondrial product. Accessed March 16 2022.https:\/\/www.ncbi.nlm.nih.gov\/nuccore\/NM_000183.3"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab051"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010009\u20101126\u20108"},{"key":"e_1_2_9_31_1","unstructured":"DGE.Richtwerte f\u00fcr die Energiezufuhr. Accessed November 14 2022.https:\/\/www.dge.de\/wissenschaft\/referenzwerte\/energie\/#mainContent"},{"key":"e_1_2_9_32_1","unstructured":"R: a language and environment for statistical computing. Version 4.1.3. The R Foundation.2022.https:\/\/www.r\u2010project.org\/"},{"key":"e_1_2_9_33_1","unstructured":"DGNS.Nationale Screeningreports Deutschland 2004\u20102020. Accessed February 9 2023.https:\/\/www.screening\u2010dgns.de\/reports.php"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102393\u20109\u20108"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404\u2010006\u20100203\u20106"},{"key":"e_1_2_9_36_1","unstructured":"G\u2010BA.Richtlinie des Gemeinsamen Bundesausschusses \u00fcber die Fr\u00fcherkennung von Krankheiten bei Kindern (Kinder\u2010Richtlinie). BAnz AT 18.08.2016 B1. Accessed November 15 2022.https:\/\/www.g\u2010ba.de\/richtlinien\/15\/"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.3.841"},{"issue":"11","key":"e_1_2_9_38_1","first-page":"2293","article-title":"Acute fatty liver of pregnancy, hemolysis, elevated liver enzymes, and low platelets syndrome, and long chain 3\u2010hydroxyacyl\u2010coenzyme a dehydrogenase deficiency","volume":"91","author":"Treem WR","year":"1996","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1026712719416"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0002\u20109378(98)70446\u20106"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381\u2010010\u20101125\u2010y"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2020.09.001"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010005\u20100545\u20104"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010018\u20100875\u20106"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2003.231"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000141967.52759.83"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2023.02.008"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12640"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2015.06.006"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1005502626406"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.06.001"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.52002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T04:38:07Z","timestamp":1713328687000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.52002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,23]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/acn3.52002"],"URL":"https:\/\/doi.org\/10.1002\/acn3.52002","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,23]]},"assertion":[{"value":"2023-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}