{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:26:29Z","timestamp":1786976789935,"version":"build-2736575974"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T00:00:00Z","timestamp":1597622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K08DK105233"],"award-info":[{"award-number":["K08DK105233"]}],"id":[{"id":"10.13039\/100000062","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":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Glutaric acidemia type 2 (GA2), also called multiple acyl\u2010CoA dehydrogenase deficiency, is an autosomal recessive disorder of fatty acid, amino acid, and choline metabolism resulting in excretion of multiple organic acids and glycine conjugates as well as elevation of various plasma acylcarnitine species (C4\u2013C18). It is caused by mutations in the\n                    <jats:italic>ETFA<\/jats:italic>\n                    ,\n                    <jats:italic>ETFB<\/jats:italic>\n                    , or\n                    <jats:italic>ETFDH<\/jats:italic>\n                    genes which are involved in the transfer of electrons from 11 flavin\u2010containing dehydrogenases to Coenzyme Q\n                    <jats:sub>10<\/jats:sub>\n                    (CoQ\n                    <jats:sub>10<\/jats:sub>\n                    ) of the mitochondrial electron transport chain (ETC). We report a patient who was originally reported as the first case with primary myopathic CoQ\n                    <jats:sub>10<\/jats:sub>\n                    deficiency when he presented at 11.5\u2009years with exercise intolerance and myopathy that improved after treatment with ubiquinone and carnitine. At age 23, his symptoms relapsed despite increasing doses of ubiquinone and he was shown to have biallelic mutations in the\n                    <jats:italic>ETFDH<\/jats:italic>\n                    gene. Treatment with riboflavin was started and ubiquinone was changed to ubiquinol. After 4 months, the patient recovered his muscle strength with normalization of laboratory exams and exercise tolerance. Functional studies on fibroblasts revealed decreased levels of ETFDH as well as of very long\u2010chain acyl\u2010CoA dehydrogenase and trifunctional protein \u03b1. In addition, the mitochondrial mass was decreased, with increased formation of reactive oxygen species and oxygen consumption rate, but with a decreased spared respiratory capacity, and decreased adenosine triphosphate level. These findings of widespread dysfunction of fatty acid oxidation and ETC enzymes support the impairment of a larger mitochondrial ETC supercomplex in our patient.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.61786","type":"journal-article","created":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T23:14:25Z","timestamp":1598570065000},"page":"2426-2431","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mitochondrial energetic impairment in a patient with late\u2010onset glutaric acidemia Type 2"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9536-3389","authenticated-orcid":false,"given":"Changrui","family":"Xiao","sequence":"first","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland 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Houston Texas USA"},{"name":"BCM\u2010CUHK Center of Medical Genetics Prince of Wales Hospital  Hong Kong SAR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Rare Disease Institute Children's National Health System  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics 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 University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"},{"name":"Department of Human Genetics University of Pittsburgh Graduate School of Public Health  Pittsburgh Pennsylvania USA"},{"name":"Center for Rare Disease Therapy UPMC Children's Hospital of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2697-1046","authenticated-orcid":false,"given":"Carlos R.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland 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