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Although in up to 95% of cases this disease is caused by <jats:italic>de novo<\/jats:italic> loss-of-function mutations in the X-linked methyl-CpG binding protein 2 gene, it is a multisystem disease associated also with mitochondrial metabolic imbalance. In addition, the presence of long QT intervals (LQT) on the patients\u2019 electrocardiograms has been associated with the development of ventricular tachyarrhythmias and sudden death. In the attempt to shed light on the mechanism underlying heart failure in RTT, we investigated the contribution of the carnitine cycle to the onset of mitochondrial dysfunction in the cardiac tissues of two subgroups of RTT mice, namely <jats:italic>Mecp2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> NQTc and <jats:italic>Mecp2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> LQTc mice, that have a normal and an LQT interval, respectively. We found that carnitine palmitoyltransferase 1\u2009A\/B and carnitine acylcarnitine translocase were significantly upregulated at mRNA and protein level in the heart of <jats:italic>Mecp2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice. Moreover, the carnitine system was imbalanced in <jats:italic>Mecp2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> LQTc mice due to decreased carnitine acylcarnitine transferase expression. By causing accumulation of intramitochondrial acylcarnitines, this imbalance exacerbated incomplete fatty acid oxidation, which, in turn, could contribute to mitochondrial overload and sudden death.<\/jats:p>","DOI":"10.1038\/srep41824","type":"journal-article","created":{"date-parts":[[2017,2,2]],"date-time":"2017-02-02T11:08:42Z","timestamp":1486033722000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Alterations in the carnitine cycle in a mouse model of Rett syndrome"],"prefix":"10.1038","volume":"7","author":[{"given":"Sabrina","family":"Mucerino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Di Salle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Alessio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Margarucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella","family":"Nicolai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariarosa A. 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