{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:52:02Z","timestamp":1783533122227,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Reduced muscle tone, muscle weakness, and physical fatigue can impact considerably on quality of life for children with neurofibromatosis type 1 (NF1). Human muscle biopsies and mouse models of NF1 deficiency in muscle show intramyocellular lipid accumulation, and preclinical data have indicated that L\u2010carnitine supplementation can ameliorate this phenotype. The aim of this study is to examine whether daily L\u2010carnitine supplementation is safe and feasible, and will improve muscle strength and reduce fatigue in children with NF1. A 12\u2010week Phase 2a trial was conducted using 1000\u2009mg daily oral levocarnitine tartrate supplementation. Recruited children were between 8 and 12\u2009years old with a clinical diagnosis of NF1, history of muscle weakness and fatigue, and na\u00efve to L\u2010carnitine. Primary outcomes were safety (self\u2010reporting, biochemical testing) and compliance. Secondary outcomes included plasma acylcarnitine profiles, functional measures (muscle strength, long jump, handwriting speed, 6\u2010minute\u2010walk test [6MWT]), and parent\u2010reported questionnaires (PedsQL\u2122, CBCL\/6\u201318). Six children completed the trial with no self\u2010reported adverse events. Biochemical tests for kidney and liver function were normal, and the average compliance was 95%. Plasma acylcarnitine levels were low, but within a range not clinically linked to carnitine deficiency. For strength measures, there was a mean 53% increase in dorsiflexion strength (95% confidence interval [CI] 8.89\u201360.75;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.02) and mean 66% increase in plantarflexion strength (95% CI 12.99\u2013134.1;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.03). In terms of muscle performance, there was a mean 10% increase in long jump distance (95% CI 2.97\u201316.03;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.01) and 6MWT distance (95% CI 5.88\u201375.45;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.03). Comparison with the 1000 Norms Project data showed a significant improvement in Z\u2010score for all of these measures. Parent reports showed no negative impact on quality of life, and the perceived benefits led to the majority of individuals remaining on L\u2010carnitine after the study. Twelve weeks of L\u2010carnitine supplementation is safe and feasible in children with NF1, and a Phase 3 trial should confirm the efficacy of treatment.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62392","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T02:43:44Z","timestamp":1624329824000},"page":"2976-2985","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["L\u2010carnitine supplementation for muscle weakness and fatigue in children with neurofibromatosis type 1: A Phase 2a clinical trial"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9547-3032","authenticated-orcid":false,"given":"Emily R.","family":"Vasiljevski","sequence":"first","affiliation":[{"name":"Orthopaedic Research &amp; Biotechnology, The Children's Hospital at Westmead  Sydney New South Wales Australia"},{"name":"Discipline of Child and Adolescent Health, Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Burns","sequence":"additional","affiliation":[{"name":"University of Sydney School of Health Sciences, Faculty of Medicine and Health  Sydney New South Wales Australia"},{"name":"Paediatric Gait Analysis Service of NSW, Sydney Children's Hospitals Network (Randwick and Westmead)  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Bray","sequence":"additional","affiliation":[{"name":"University of Sydney School of Health Sciences, Faculty of Medicine and Health  Sydney New South Wales Australia"},{"name":"Kids Neuroscience Centre, The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Donlevy","sequence":"additional","affiliation":[{"name":"University of Sydney School of Health Sciences, Faculty of Medicine and Health  Sydney New South Wales Australia"},{"name":"Kids Neuroscience Centre, The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita J.","family":"Mudge","sequence":"additional","affiliation":[{"name":"Paediatric Gait Analysis Service of NSW, Sydney Children's Hospitals Network (Randwick and Westmead)  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristi J.","family":"Jones","sequence":"additional","affiliation":[{"name":"Discipline of Child and Adolescent Health, Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"},{"name":"Kids Neuroscience Centre, The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Summers","sequence":"additional","affiliation":[{"name":"Healthy Ageing Theme The Garvan Institute of Medical Research  Darlinghurst New South Wales Australia"},{"name":"St Vincent's Clinical School, Faculty of Medicine University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3443-9359","authenticated-orcid":false,"given":"Andrew","family":"Biggin","sequence":"additional","affiliation":[{"name":"Institute of Endocrinology and Diabetes University of Sydney, The Children's Hospital at Westmead  Sydney New South Wales Australia"},{"name":"The Children's Hospital at Westmead Clinical School The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig F.","family":"Munns","sequence":"additional","affiliation":[{"name":"Institute of Endocrinology and Diabetes University of Sydney, The Children's Hospital at Westmead  Sydney New South Wales Australia"},{"name":"The Children's Hospital at Westmead Clinical School The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8126-3579","authenticated-orcid":false,"given":"Marnee J.","family":"McKay","sequence":"additional","affiliation":[{"name":"University of Sydney School of Health Sciences, Faculty of Medicine and Health  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7830-7270","authenticated-orcid":false,"given":"Jennifer","family":"Cartwright","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medicine The University of Newcastle  Newcastle New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3684-9770","authenticated-orcid":false,"given":"David G.","family":"Little","sequence":"additional","affiliation":[{"name":"Orthopaedic Research &amp; Biotechnology, The Children's Hospital at Westmead  Sydney New South Wales Australia"},{"name":"Discipline of Child and Adolescent Health, Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7757-6281","authenticated-orcid":false,"given":"Aaron","family":"Schindeler","sequence":"additional","affiliation":[{"name":"Orthopaedic Research &amp; Biotechnology, The Children's Hospital at Westmead  Sydney New South Wales Australia"},{"name":"Discipline of Child and Adolescent Health, Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-139X.2001.00055.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2015-210727"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2214.2006.00717.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1983.63.4.1420"},{"key":"e_1_2_9_6_1","first-page":"91","volume-title":"In: Developing Norm\u2010Referenced Standardized Tests","author":"Cermak S.","year":"1989"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12777"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.bpb.0000271310.87997.ae"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389901400306"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307380201700802"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.881792"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/2333794X19830696"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)93426-P"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2011_36"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24234262"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physio.2014.12.002"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0958-2592(03)00047-6"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000166711"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-018-0829-3"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000183087"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.33.1.2"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00058"},{"issue":"5","key":"e_1_2_9_23_1","article-title":"Mitochondrial dysfunction in autism Spectrum disorders","volume":"6","author":"Siddiqui M. F.","year":"2016","journal-title":"Autism Open Access"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.125799"},{"issue":"2","key":"e_1_2_9_25_1","first-page":"161","article-title":"Skeletal muscle and motor deficits in Neurofibromatosis type 1","volume":"15","author":"Summers M. A.","year":"2015","journal-title":"Journal of Musculoskeletal & Neuronal Interactions"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx423"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/3232105"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.84.1.58"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2018.08.001"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpc.14764"},{"key":"e_1_2_9_31_1","volume-title":"The Handwriting Speed Test","author":"Wallen M. A.","year":"1996"},{"key":"e_1_2_9_32_1","volume-title":"Wechsler intelligence scale for children\u2010Revised edition","author":"Wechsler D.","year":"1974"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2016.01.020"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00390.x"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62392","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62392","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62392","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:54:26Z","timestamp":1773226466000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,21]]},"references-count":33,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/ajmg.a.62392"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62392","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,21]]},"assertion":[{"value":"2020-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}