title: Expanding the clinical phenotype of the mitochondrial m.13513G>A mutation with the first report of a fatal neonatal presentation.
abstract: Diagnosis of mitochondrial disease is often a challenge because of the extreme heterogeneity of the clinical phenotype and the variety of underlying gene defects. Insight into the range of clinical phenotypes associated with a particular mitochondrial DNA mutation will facilitate better recognition of patients at risk by focused gene testing. We present a family affected by the mitochondrial m.13513G>A (p.D393N, ND5) mutation, illustrating a previously unreported degree of clinical heterogeneity, varying from mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) in a 10-year-old female, to a fatal neonatal course with metabolic acidosis and hypotonia in a younger sister, to absence of medical problems in the mother. The mutation loads ranging from 66% in the deceased neonate to 30% in the female with MELAS and 7% in the asymptomatic mother, correlated with severity of the clinical phenotype. The importance of proactive collection and storage of appropriate samples during the diagnostic work-up of an acutely ill or deceased neonate, allowing subsequent mitochondrial investigations, is hereby illustrated.
authors.affiliation: Division of Biochemical Diseases, Department of Pediatrics, British Columbia Children's Hospital/University of British Columbia, Vancouver, BC, Canada.
authors.forename: Clara D M
authors.initials: CD
authors.lastname: Van Karnebeek
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Waters
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sargent
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mezei
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mezey
authors.forename: Lee-Jun
authors.initials: LJ
authors.lastname: Wong
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Sylvia
authors.initials: S
authors.lastname: Stöckler-Ipsiroglu
mesh_terms: D000328:Adult; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D017241:MELAS Syndrome / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype
chemical_list: D004272:DNA, Mitochondrial