{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:46:40Z","timestamp":1785836800872,"version":"3.56.0"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["15\u2010HG\u20100130"],"award-info":[{"award-number":["15\u2010HG\u20100130"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Multiple Acyl\u2010CoA Dehydrogenase Deficiency (MADD) is an autosomal recessive inborn error of metabolism caused by biallelic pathogenic variants in one of three known genes:\n                    <jats:italic>ETFA<\/jats:italic>\n                    ,\n                    <jats:italic>ETFB<\/jats:italic>\n                    , and\n                    <jats:italic>ETFDH<\/jats:italic>\n                    . It can cause multisystem dysfunction, including cardiomyopathy in severe cases. Ketone supplementation has been reported to be beneficial in a few case reports, but its long\u2010term effectiveness remains unclear. We report an infant with a clinical and biochemical diagnosis of MADD who showed a favorable response to ketone supplementation, with marked improvement in severe cardiac dysfunction and sustained near\u2010normal cardiac function and biochemical profiles over 3.5\u2009years. Although genome sequencing did not identify causative variants, RNA sequencing revealed reduced\n                    <jats:italic>ETFB<\/jats:italic>\n                    transcript levels, and western blot analysis showed decreased ETFB protein levels. This case report illustrates MADD without an identified molecular diagnosis and provides evidence that near\u2010absent ETFB expression is likely responsible for his presentation. These observations can guide further studies investigating the transcriptional regulation of\n                    <jats:italic>ETFB<\/jats:italic>\n                    , thereby elucidating an underappreciated molecular mechanism underlying MADD. Initiating metabolic therapy in patients with clinically suspected MADD, even in the absence of a confirmed molecular diagnosis, can be beneficial as suggested by the clinical and biochemical responses to our therapeutic trial.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70177","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T07:49:00Z","timestamp":1777276140000},"page":"2140-2150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Response of an Infant With Presumed Multiple Acyl\u2010\n                    <scp>CoA<\/scp>\n                    Dehydrogenase Deficiency (\n                    <scp>MADD<\/scp>\n                    ) to Ketone Supplementation"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7278-8242","authenticated-orcid":false,"given":"Yutaka","family":"Furuta","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn N.","family":"Bloom","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetic and Genomic Medicine University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Vockley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetic and Genomic Medicine University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela R.","family":"Grochowsky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neena S.","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen W.","family":"Strickler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie N.","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica T.","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3015-3529","authenticated-orcid":false,"given":"B. Lakshitha A.","family":"Perera","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Genetic Medicine and Clinical Pharmacology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4204-8734","authenticated-orcid":false,"given":"Eric R.","family":"Gamazon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Genetic Medicine and Clinical Pharmacology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynette C.","family":"Rives","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center  Nashville Tennessee 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