title: Expanding the Clinical Spectrum of Mitochondrial Citrate Carrier (SLC25A1) Deficiency: Facial Dysmorphism in Siblings with Epileptic Encephalopathy and Combined D,L-2-Hydroxyglutaric Aciduria.
abstract: Recessive mutations in SLC25A1 encoding mitochondrial citrate carrier cause a rare inherited metabolic disorder, combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA), characterized by epileptic encephalopathy, respiratory insufficiency, developmental arrest and early death. Here, we describe two siblings compound heterozygotes for null/missense SLC25A1 mutations, c.18_24dup (p.Ala9Profs*82), and c.134C>T (p.Pro45Leu). These children presented with classic clinical features of D,L-2-HGA, but also showed marked facial dysmorphism. Additionally, there was prominent lactic acidosis in one of the siblings. Our observations suggest that facial dysmorphism is a previously unrecognized but an important diagnostic feature of SLC25A1 deficiency and expand the clinical phenotype linked to SLC25A1 mutations.
authors.affiliation: Divison of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, 27710, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Prasun
authors.forename: Sarah
authors.initials: S
authors.lastname: Young
authors.forename: Gajja
authors.initials: G
authors.lastname: Salomons
authors.forename: Andrea
authors.initials: A
authors.lastname: Werneke
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Jiang
authors.forename: Eduard
authors.initials: E
authors.lastname: Struys
authors.forename: Mikell
authors.initials: M
authors.lastname: Paige
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Avantaggiati
authors.forename: Marie
authors.initials: M
authors.lastname: McDonald