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With approximately 30 patients reported to date, DLD deficiency was associated with three major clinical presentations: an early\u2010onset encephalopathic phenotype with metabolic acidosis, a predominantly hepatic presentation with liver failure, and a rare myopathic phenotype. To elucidate the demographic, phenotypic, and molecular characteristics of patients with DLD deficiency within the Israeli population, data were collected from metabolic disease specialists in four large tertiary medical centers in the center and south of Israel. Pediatric and adult patients with biallelic variants in <jats:italic>DLD<\/jats:italic> were included in the study. A total of 53 patients of 35 families were included in the cohort. Age at presentation ranged between birth and 10\u2009years. Wide phenotypic variability was observed, from asymptomatic individuals in their sixth decade of life, to severe, neonatal\u2010onset disease with devastating neurological sequelae. Six <jats:italic>DLD<\/jats:italic> variants were noted, the most common of which was the c.685G&gt;T (p.G229C) variant in homozygous form (24\/53 patients, 45.3%; 13\/35 families), observed mostly among patients of Ashkenazi\u2010Jewish descent, followed by the homozygous c.1436A&gt;T (p.D479V) variant, found in 20 patients of Bedouin descent (37.7%; 16\/35 families). Overall, patients did not necessarily present as one of the previously described distinct clinical phenotypes. DLD deficiency is a panethnic disorder, with significant phenotypic variability, and comprises a continuum, rather than three distinct clinical presentations.<\/jats:p>","DOI":"10.1002\/jimd.12778","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T08:10:23Z","timestamp":1721722223000},"page":"895-902","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The natural history of dihydrolipoamide dehydrogenase deficiency in Israel"],"prefix":"10.1002","volume":"47","author":[{"given":"Ben","family":"Pode\u2010Shakked","sequence":"first","affiliation":[{"name":"Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital Sheba Medical Center  Tel\u2010Hashomer Israel"},{"name":"School of Medicine, Faculty of Medical and Health Sciences Tel\u2010Aviv University  Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval 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