{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:02:01Z","timestamp":1769731321313,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["Veni grant 91617021"],"award-info":[{"award-number":["Veni grant 91617021"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Isobutyryl\u2010CoA dehydrogenase (IBD) is a mitochondrial enzyme catalysing the third step in the degradation of the essential branched\u2010chain amino acid valine and is encoded by <jats:italic>ACAD8<\/jats:italic>. <jats:italic>ACAD8<\/jats:italic> mutations lead to isobutyryl\u2010CoA dehydrogenase deficiency (IBDD), which is identified by increased C4\u2010acylcarnitine levels. Affected individuals are either asymptomatic or display a variety of symptoms during infancy, including speech delay, cognitive impairment, failure to thrive, hypotonia, and emesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we review all previously published IBDD patients and describe a girl diagnosed with IBDD who was presenting with autism as the main disease feature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>To assess whether a phenotype\u2010genotype correlation exists that could explain the development or absence of clinical symptoms in IBDD, we compared CADD scores, in silico mutation predictions, LoF tolerance scores and C4\u2010acylcarnitine levels between symptomatic and asymptomatic individuals. Statistical analysis of these parameters did not establish significant differences amongst both groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>As in our proband, trio whole exome sequencing did not establish an alternative secondary genetic diagnosis for autism, and reported long\u2010term follow\u2010up of IBDD patients is limited, it is possible that autism spectrum disorders could be one of the disease\u2010associated features. Further long\u2010term follow\u2010up is suggested in order to delineate the full clinical spectrum associated with IBDD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1595","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T06:59:12Z","timestamp":1610693952000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Isobutyryl\u2010CoA dehydrogenase deficiency associated with autism in a girl without an alternative genetic diagnosis by trio whole exome sequencing: A case report"],"prefix":"10.1002","volume":"9","author":[{"given":"Maria","family":"Eleftheriadou","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Erasmus MC University Medical Center Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evita","family":"Medici\u2010 van den Herik","sequence":"additional","affiliation":[{"name":"Department of Neurology Erasmus MC University Medical Center Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyra","family":"Stuurman","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus MC University Medical Center Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yolande","family":"van Bever","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus MC University Medical Center Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debby M. 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