{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:06:56Z","timestamp":1790276816032,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mitochondrial trifunctional protein (MTP) is involved in long\u2010chain fatty acid \u03b2\u2010oxidation (lcFAO). Deficiency of one or more of the enzyme activities as catalyzed by MTP causes generalized MTP deficiency (MTPD), long\u2010chain hydroxyacyl\u2010CoA dehydrogenase deficiency (LCHADD), or long\u2010chain ketoacyl\u2010CoA thiolase deficiency (LCKATD). When genetic variants result in thermo\u2010sensitive enzymes, increased body temperature (e.g. fever) can reduce enzyme activity and be a risk factor for clinical decompensation. This is the first description of five patients with a thermo\u2010sensitive MTP deficiency. Clinical and genetic information was obtained from clinical files. Measurement of LCHAD and LCKAT activities, lcFAO\u2010flux studies and palmitate loading tests were performed in skin fibroblasts cultured at 37\u00b0C and 40\u00b0C. In all patients (four MTPD, one LCKATD), disease manifested during childhood (manifestation age: 2\u201310\u2009years) with myopathic symptoms triggered by fever or exercise. In four patients, signs of retinopathy or neuropathy were present. Plasma long\u2010chain acylcarnitines were normal or slightly increased. <jats:italic>HADHB<\/jats:italic> variants were identified (at age: 6\u201318\u2009years) by whole exome sequencing or gene panel analyses. At 37\u00b0C, LCHAD and LCKAT activities were mildly impaired and lcFAO\u2010fluxes were normal. Remarkably, enzyme activities and lcFAO\u2010fluxes were markedly diminished at 40\u00b0C. Preventive (dietary) measures improved symptoms for most. In conclusion, all patients with thermo\u2010sensitive MTP deficiency had a long diagnostic trajectory and both genetic and enzymatic testing were required for diagnosis. The frequent absence of characteristic acylcarnitine abnormalities poses a risk for a diagnostic delay. Given the positive treatment effects, upfront genetic screening may be beneficial to enhance early recognition.<\/jats:p>","DOI":"10.1002\/jimd.12503","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T10:44:10Z","timestamp":1649673850000},"page":"819-831","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Thermo\u2010sensitive mitochondrial trifunctional protein deficiency presenting with episodic myopathy"],"prefix":"10.1002","volume":"45","author":[{"given":"Marit","family":"Schwantje","sequence":"first","affiliation":[{"name":"Department of Metabolic Diseases Wilhelmina Children's Hospital, University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merel S.","family":"Ebberink","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Doolaard","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos P. 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