{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:58:56Z","timestamp":1790974736495,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005941","name":"Dietmar Hopp Stiftung","doi-asserted-by":"publisher","award":["23011235"],"award-info":[{"award-number":["23011235"]}],"id":[{"id":"10.13039\/501100005941","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["GENOMIT I6478\u2010B"],"award-info":[{"award-number":["GENOMIT I6478\u2010B"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Dihydrolipoamide dehydrogenase deficiency (MIM 246900\/DLDD) is an autosomal recessive mitochondrial disease with three clinical subgroups. The hepatic form leads to recurrent metabolic decompensations often accompanied by elevated levels of liver transaminases (ELT) in blood, sometimes progressing to acute liver failure (ALF). Genetically, it is linked to the p.G229C variant in the\n                    <jats:italic>DLD<\/jats:italic>\n                    gene, which has been reported in the Ashkenazi Jewish and Arabic population. In this study, we analyzed phenotypic diversity, therapeutic management, and outcome in novel symptomatic individuals with hepatic DLDD identified by whole exome sequencing (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097) in Central Europe as well as in previously reported cases (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200945). Fifty\u2010one of 52 DLDD patients carried the p.G229C variant (39 in a homozygous state). During decompensations, precipitated by febrile infectious disease or fasting, affected individuals presented with nausea, vomiting, abdominal pain, hepatomegaly, hypoglycemia, and lactic acidosis. In individuals homozygous for the p.G229C variant, neurologic manifestations were rare, whereas mild neurologic symptoms were found in individuals (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098) carrying a different\n                    <jats:italic>DLD<\/jats:italic>\n                    variant\n                    <jats:italic>in trans<\/jats:italic>\n                    . During decompensation, levels of specific plasma amino acids like citrulline or branched\u2010chain amino acids, and urinary organic acids, like 2\u2010oxoglutaric acid, were frequently elevated. However, known biomarkers\u2014with the exception of lactate\u2014were not consistently elevated during these episodes and typically normal in the interval, highlighting the usefulness of early genetic testing in all children with unexplained ELT or ALF to reduce the time to diagnosis. While there exists consensus for rescue therapy with intravenous glucose during decompensations and maintenance therapy with riboflavin, therapies with thiamine and antioxidants (e.g., N\u2010acetylcysteine) were reported to be useful in single individuals with recurrent decompensations.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70035","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:23:49Z","timestamp":1747722229000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Hepatic Form of Dihydrolipoamide Dehydrogenase Deficiency (\n                    <scp>DLDD<\/scp>\n                    ): Phenotypic Spectrum, Laboratory Findings, and Therapeutic Approaches in 52 Patients"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3887-2168","authenticated-orcid":false,"given":"Nicole","family":"Hammann","sequence":"first","affiliation":[{"name":"Heidelberg University, Medical Faculty, University Hospital Heidelberg, Center for Child and Adolescent Medicine Division of Pediatric Neurology and Metabolic Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1403-9075","authenticated-orcid":false,"given":"Christian","family":"Staufner","sequence":"additional","affiliation":[{"name":"Heidelberg University, Medical Faculty, University Hospital Heidelberg, Center for Child and Adolescent Medicine Division of Pediatric Neurology and Metabolic Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea Dewi","family":"Schlieben","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health Technical University of Munich  Munich Germany"},{"name":"Institute of Human Genetics Helmholtz Zentrum Munich  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antal","family":"Dezs\u0151fi\u2010Gottl","sequence":"additional","affiliation":[{"name":"B\u00f3kay Street Department, Pediatric Centre Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4215-8258","authenticated-orcid":false,"given":"Ren\u00e9 G.","family":"Feichtinger","sequence":"additional","affiliation":[{"name":"University Children's Hospital Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU)  Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"H\u00e4berle","sequence":"additional","affiliation":[{"name":"University Children's Hospital Zurich and Children's Research Center  Zurich 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"McLin","sequence":"additional","affiliation":[{"name":"Swiss Pediatric Liver Center Geneva University Hospitals Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Rymen","sequence":"additional","affiliation":[{"name":"Center for Metabolic Diseases, Department of Paediatrics University Hospitals Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Slavetinsky","sequence":"additional","affiliation":[{"name":"Paediatric Surgery and Urology University Children's Hospital T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Sturm","sequence":"additional","affiliation":[{"name":"Paediatric Gastroenterology and Hepatology University Children's Hospital T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6970-336X","authenticated-orcid":false,"given":"Johannes A.","family":"Mayr","sequence":"additional","affiliation":[{"name":"University Children's Hospital Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU)  Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matias","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health Technical University of Munich  Munich Germany"},{"name":"Institute of Human Genetics Helmholtz Zentrum Munich  Neuherberg Germany"},{"name":"Department Computational Health, Institute of Neurogenomics Helmholtz Zentrum M\u00fcnchen  Munich 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Medical Faculty, University Hospital Heidelberg, Center for Child and Adolescent Medicine Division of Pediatric Neurology and Metabolic Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9561-8190","authenticated-orcid":false,"given":"Dominic","family":"Lenz","sequence":"additional","affiliation":[{"name":"Heidelberg University, Medical Faculty, University Hospital Heidelberg, Center for Child and Adolescent Medicine Division of Pediatric Neurology and Metabolic Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450\u2010197712000\u201000006"},{"key":"e_1_2_11_3_1","volume-title":"GeneReviews()","author":"Quinonez S. 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