Improved lactate control with dichloroacetate in a case with severe neonatal lactic acidosis due to MTFMT mitochondrial translation disorder

Jennifer Bennett; Marina Kerr; Steven C Greenway; Marisa W Friederich; Johan L K Van Hove; Dustin Hittel; Aneal Khan

doi:10.1016/j.ymgmr.2020.100616

Improved lactate control with dichloroacetate in a case with severe neonatal lactic acidosis due to MTFMT mitochondrial translation disorder

Mol Genet Metab Rep. 2020 Jun 15:24:100616. doi: 10.1016/j.ymgmr.2020.100616. eCollection 2020 Sep.

Authors

Jennifer Bennett¹, Marina Kerr¹, Steven C Greenway², Marisa W Friederich^{3

4}, Johan L K Van Hove^{3

4}, Dustin Hittel⁵, Aneal Khan¹

Affiliations

¹ Department of Medical Genetics and Pediatrics, Alberta Children's Hospital, Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
² Departments of Pediatrics, Cardiac Sciences, Biochemistry & Molecular Biology, Alberta Children's Hospital Research Institute, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
³ Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Aurora, CO, USA.
⁴ Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO, USA.
⁵ Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Abstract

Mitochondrial methionyl-tRNA formyltransferase (MTFMT) is a nuclear-encoded gene that produces a protein involved in mitochondrial translation. MTFMT formylates a portion of Met-tRNA^Met, which allows for translation initiation of mitochondrial mRNA. Mutations in this gene have been shown to result in decreased mitochondrial translation with reduction function of the electron transport chain complexes I, III, IV, and V, thus affecting cellular energy production. Our patient presented with severe lactic acidosis in the neonatal period, and was found to be homozygous for the pathogenic mutation c.994C > T, p.(Arg332*). Her blood lactate levels normalized and her cardiomyopathy reversed after initiation of dichloroacetate (30 mg/kg/day). After two years of follow-up, she continues to show long-term lactate stability, continues to make developmental gains, and is in overall good general health. This is the first report using dichloroacetate in a patient with MTFMT deficiency, which may be a potential therapeutic option that warrants further study.

Keywords: Cardiomyopathy; Congenital lactic acidosis; Dichloroacetate; Hutterite; MTFMT; Mitochondrial disorder.

Publication types

Case Reports