PT  - JOURNAL ARTICLE
AU  - Emanuele Barca
AU  - Yuelin Long
AU  - Victoria Cooley
AU  - Robert Schoenaker
AU  - Valentina Emmanuele
AU  - Salvatore DiMauro
AU  - Bruce H. Cohen
AU  - Amel Karaa
AU  - Georgirene D. Vladutiu
AU  - Richard Haas
AU  - Johan L.K. Van Hove
AU  - Fernando Scaglia
AU  - Sumit Parikh
AU  - Jirair K. Bedoyan
AU  - Susanne D. DeBrosse
AU  - Ralitza H. Gavrilova
AU  - Russell P. Saneto
AU  - Gregory M. Enns
AU  - Peter W. Stacpoole
AU  - Jaya Ganesh
AU  - Austin Larson
AU  - Zarazuela Zolkipli-Cunningham
AU  - Marni J. Falk
AU  - Amy C. Goldstein
AU  - Mark Tarnopolsky
AU  - Andrea Gropman
AU  - Kathryn Camp
AU  - Danuta Krotoski
AU  - Kristin Engelstad
AU  - Xiomara Q. Rosales
AU  - Joshua Kriger
AU  - Johnston Grier
AU  - Richard Buchsbaum
AU  - John L.P. Thompson
AU  - Michio Hirano
TI  - Mitochondrial diseases in North America
AID  - 10.1212/NXG.0000000000000402
DP  - 2020 Apr 01
TA  - Neurology Genetics
PG  - e402
VI  - 6
IP  - 2
4099  - http://ng.neurology.org/content/6/2/e402.short
4100  - http://ng.neurology.org/content/6/2/e402.full
SO  - Neurol Genet2020 Apr 01; 6
AB  - Objective To describe clinical, biochemical, and genetic features of participants with mitochondrial diseases (MtDs) enrolled in the North American Mitochondrial Disease Consortium (NAMDC) Registry.Methods This cross-sectional, multicenter, retrospective database analysis evaluates the phenotypic and molecular characteristics of participants enrolled in the NAMDC Registry from September 2011 to December 2018. The NAMDC is a network of 17 centers with expertise in MtDs and includes both adult and pediatric specialists.Results One thousand four hundred ten of 1,553 participants had sufficient clinical data for analysis. For this study, we included only participants with molecular genetic diagnoses (n = 666). Age at onset ranged from infancy to adulthood. The most common diagnosis was multisystemic disorder (113 participants), and only a minority of participants were diagnosed with a classical mitochondrial syndrome. The most frequent classical syndromes were Leigh syndrome (97 individuals) and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (71 individuals). Pathogenic variants in the mitochondrial DNA were more frequently observed (414 participants) than pathogenic nuclear gene variants (252 participants). Pathogenic variants in 65 nuclear genes were identified, with POLG1 and PDHA1 being the most commonly affected. Pathogenic variants in 38 genes were reported only in single participants.Conclusions The NAMDC Registry data confirm the high variability of clinical, biochemical, and genetic features of participants with MtDs. This study serves as an important resource for future enhancement of MtD research and clinical care by providing the first comprehensive description of participant with MtD in North America.CoQ10=coenzyme Q10; COX=cytochrome c oxidase; cPEO=chronic progressive external ophthalmoplegia; IRB=institutional review board; LS=Leigh syndrome; LHON=Leber hereditary optic neuropathy; MELAS=mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; MERRF=myoclonus epilepsy with ragged red fibers; MtD=mitochondrial disease; mtDNA=mitochondrial DNA; NAMDC=North American Mitochondrial Disease Consortium; nDNA=nuclear DNA; OxPhos=oxidative phosphorylation; PDC=pyruvate dehydrogenase complex; SLE=stroke-like episode; TP=thymidine phosphorylase