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Malate dehydrogenase 2 deficiency is an emerging cause of pediatric epileptic encephalopathy with a recognizable biochemical signature.
Priestley, Jessica R C; Pace, Lisa M; Sen, Kuntal; Aggarwal, Anjali; Alves, Cesar Augusto P F; Campbell, Ian M; Cuddapah, Sanmati R; Engelhardt, Nicole M; Eskandar, Marina; Jolín García, Paloma C; Gropman, Andrea; Helbig, Ingo; Hong, Xinying; Gowda, Vykuntaraju K; Lusk, Laina; Trapane, Pamela; Srinivasan, Varunvenkat M; Suwannarat, Pim; Ganetzky, Rebecca D.
Afiliación
  • Priestley JRC; Section of Biochemical Genetics, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Pace LM; Department of Pediatrics, University of Florida College of Medicine, Jacksonville, FL, USA.
  • Sen K; Division of Neurogenetics and Neurodevelopmental Pediatrics, Children's National Hospital, Washington D.C., USA.
  • Aggarwal A; Division of Genetics and Metabolism, University of Minnesota, Minneapolis, MN, USA.
  • Alves CAPF; Division of Neuroradiology, Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, USA.
  • Campbell IM; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Cuddapah SR; Section of Biochemical Genetics, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Engelhardt NM; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Eskandar M; Section of Biochemical Genetics, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Jolín García PC; Mitochondrial Medicine, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Gropman A; Division of Child Neurology, Children's National Hospital, Washington D.C., USA.
  • Helbig I; Section of Biochemical Genetics, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Hong X; Division of Neurogenetics and Neurodevelopmental Pediatrics, Children's National Hospital, Washington D.C., USA.
  • Gowda VK; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Lusk L; Epilepsy Neurogenetics Initiative, Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Trapane P; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Srinivasan VM; Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India.
  • Suwannarat P; Epilepsy Neurogenetics Initiative, Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Ganetzky RD; Division of Pediatric Genetics, Department of Genetics, University of Florida College of Medicine, Jacksonville, FL, USA.
Mol Genet Metab Rep ; 33: 100931, 2022 Dec.
Article en En | MEDLINE | ID: mdl-36420423
Malate dehydrogenases (MDH) serve a critical role in maintaining equilibrium of the NAD+/NADH ratio between the mitochondria and cytosol through the catalysis of the oxidation of L-malate to oxaloacetate in a reversible, NADH-dependent manner. MDH2 encodes the mitochondrial isoform, which is integral to the tricarboxylic acid cycle and thus energy homeostasis. Recently, five patients harboring compound heterozygous MDH2 variants have been described, three with early-onset epileptic encephalopathy, one with a stroke-like episode, and one with dilated cardiomyopathy. Here, we describe an additional seven patients with biallelic variants in MDH2, the largest and most neurodevelopmentally and ethnically diverse cohort to-date, including homozygous variants, a sibling pair, non-European patients, and an adult. From these patients, we learn that MDH2 deficiency results in a biochemical signature including elevations of plasma lactate and the lactate:pyruvate ratio with urinary excretion of malate. It also results in a recognizable constellation of neuroimaging findings of anterior-predominant cerebral atrophy, subependymal cysts with ventricular septations. We also recognize MDH2 deficiency as a cause of Leigh syndrome. Taken with existing patient reports, we conclude that MDH2 deficiency is an emerging and likely under-recognized cause of infantile epileptic encephalopathy and provide a framework for medical evaluation of patients identified with biallelic MDH2 variants.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Genet Metab Rep Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Genet Metab Rep Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos