{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:50:56Z","timestamp":1761745856503,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a rare autosomal recessive long-chain fatty acid oxidation disorder caused by mutations in the ACADVL gene. The myopathic form presents with exercise intolerance, exercise-related rhabdomyolysis, and muscle pain, usually starting during adolescence or adulthood. We report on a 17-year-old boy who has presented with exercise-induced muscle pain and fatigue since childhood. In recent clinical history, episodes of exercise-related severe hyperCKemia and myoglobinuria were reported. Electromyography was normal, and a muscle biopsy showed only \u201cmoth-eaten\u201d fibers, and a mild increase in lipid storage in muscle fibers. NGS analysis displayed the already known heterozygote c.1769G&gt;A variant and the unreported heterozygote c.523G&gt;C change in ACADVL both having disease-causing predictions. Plasma acylcarnitine profiles revealed high long-chain acylcarnitine species levels, especially C14:1. Clinical, histopathological, biochemical, and genetic tests supported the diagnosis of VLCAD deficiency. Our report of a novel pathogenic missense variant in ACADVL expands the allelic heterogeneity of the disease. Since dietary treatment is the only therapy available for treating VLCAD deficiency and it is more useful the earlier it is started, prompt diagnosis is essential in order to minimize muscle damage and slow the disease progression.<\/jats:p>","DOI":"10.3390\/brainsci13081178","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:26:39Z","timestamp":1691497599000},"page":"1178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Juvenile-Onset Recurrent Rhabdomyolysis Due to Compound Heterozygote Variants in the ACADVL Gene"],"prefix":"10.3390","volume":"13","author":[{"given":"Beatrice","family":"Labella","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Sciences, University of Brescia, 25100 Brescia, Italy"},{"name":"Unit of Neurology, ASST \u201cSpedali Civili\u201d, 25100 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaetana","family":"Lanzi","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, Diagnostic Department, ASST-Pedali Civili of Brescia, 25100 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Cotti Piccinelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, University of Brescia, 25100 Brescia, Italy"},{"name":"NeMO\u2014Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filomena","family":"Caria","sequence":"additional","affiliation":[{"name":"NeMO\u2014Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0465-5262","authenticated-orcid":false,"given":"Simona","family":"Damioli","sequence":"additional","affiliation":[{"name":"NeMO\u2014Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Risi","sequence":"additional","affiliation":[{"name":"NeMO\u2014Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrica","family":"Bertella","sequence":"additional","affiliation":[{"name":"NeMO\u2014Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loris","family":"Poli","sequence":"additional","affiliation":[{"name":"Unit of Neurology, ASST \u201cSpedali Civili\u201d, 25100 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Padovani","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, University of Brescia, 25100 Brescia, Italy"},{"name":"Unit of Neurology, ASST \u201cSpedali Civili\u201d, 25100 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2852-7512","authenticated-orcid":false,"given":"Massimiliano","family":"Filosto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, University of Brescia, 25100 Brescia, Italy"},{"name":"NeMO\u2014Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Amemiya, A. 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A"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/13\/8\/1178\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:28:14Z","timestamp":1760128094000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/13\/8\/1178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,8]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["brainsci13081178"],"URL":"https:\/\/doi.org\/10.3390\/brainsci13081178","relation":{},"ISSN":["2076-3425"],"issn-type":[{"type":"electronic","value":"2076-3425"}],"subject":[],"published":{"date-parts":[[2023,8,8]]}}}