{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:39:36Z","timestamp":1790962776385,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,4,19]],"date-time":"2016-04-19T00:00:00Z","timestamp":1461024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Stichting ParkinsonFonds (The Netherlands)"},{"name":"Slovak Scientific Grant Agency","award":["VEGA 1\/0724\/15"],"award-info":[{"award-number":["VEGA 1\/0724\/15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>ECHS1<\/jats:italic> encodes a mitochondrial enzyme involved in the degradation of essential amino acids and fatty acids. Recently, <jats:italic>ECHS1<\/jats:italic> mutations were shown to cause a new severe metabolic disorder presenting as Leigh or Leigh\u2010like syndromes. The objective of this study was to describe a family with 2 siblings affected by different dystonic disorders as a resulting phenotype of <jats:italic>ECHS1<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical evaluation, MRI imaging, genome\u2010wide linkage, exome sequencing, urine metabolite profiling, and protein expression studies were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The first sibling is 17 years old and presents with generalized dystonia and severe bilateral pallidal MRI lesions after 1 episode of infantile subacute metabolic encephalopathy (Leigh\u2010like syndrome). In contrast, the younger sibling (15 years old) only suffers from paroxysmal exercise\u2010induced dystonia and has very mild pallidal MRI abnormalities. Both patients carry compound heterozygous <jats:italic>ECHS1<\/jats:italic> mutations: c.232G&gt;T (predicted protein effect: p.Glu78Ter) and c.518C&gt;T (p.Ala173Val). Linkage analysis, exome sequencing, cosegregation, expression studies, and metabolite profiling support the pathogenicity of these mutations. Expression studies in patients' fibroblasts showed mitochondrial localization and severely reduced levels of ECHS1 protein. Increased urinary S\u2010(2\u2010carboxypropyl)cysteine and N\u2010acetyl\u2010S\u2010(2\u2010carboxypropyl)cysteine levels, proposed metabolic markers of this disorder, were documented in both siblings. Sequencing <jats:italic>ECHS1<\/jats:italic> in 30 unrelated patients with paroxysmal dyskinesias revealed no further mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The phenotype associated with <jats:italic>ECHS1<\/jats:italic> mutations might be milder than reported earlier, compatible with prolonged survival, and also includes isolated paroxysmal exercise\u2010induced dystonia. <jats:italic>ECHS1<\/jats:italic> screening should be considered in patients with otherwise unexplained paroxysmal exercise\u2010induced dystonia, in addition to those with Leigh and Leigh\u2010like syndromes. Diet regimens and detoxifying agents represent potential therapeutic strategies. \u00a9 2016 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.26610","type":"journal-article","created":{"date-parts":[[2016,4,19]],"date-time":"2016-04-19T03:41:38Z","timestamp":1461037298000},"page":"1041-1048","source":"Crossref","is-referenced-by-count":76,"title":["Paroxysmal exercise\u2010induced dystonia within the phenotypic spectrum of <i>ECHS1<\/i> deficiency"],"prefix":"10.1002","volume":"31","author":[{"given":"Simone","family":"Olgiati","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matej","family":"Skorvanek","sequence":"additional","affiliation":[{"name":"Department of Neurology Safarik University Kosice Slovakia"},{"name":"Department of Neurology University Hospital L. 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