title: Unique presentation of LHON/MELAS overlap syndrome caused by m.13046T>C in MTND5.
abstract: Leber hereditary optic neuropathy (LHON) and mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes (MELAS) syndromes are mitochondrially inherited disorders characterized by acute visual failure and variable multiorgan system presentation, respectively.
  
  
  
  A 12-year-old girl with otherwise unremarkable medical history presented with abrupt, painless loss of vision. Over the next few months, she developed moderate sensorineural hearing loss, vertigo, migraines, anhedonia and thyroiditis. Ocular examination confirmed bilateral optic nerve atrophy. Metabolic workup documented elevated cerebrospinal fluid lactate. Initial genetic analyses excluded the three most common LHON mutations. Subsequently, Sanger sequencing of the entire mitochondrial DNA (mtDNA) genome was performed.
  
  
  
  Whole mtDNA sequencing revealed a pathogenic heteroplasmic mutation m.13046T>C in MTND5 encoding the ND5 subunit of complex I. This particular variant has previously been described in a single case report of MELAS/Leigh syndrome (subacute necrotizing encephalopathy). Based on the constellation of clinical symptoms in our patient, we diagnose the condition as LHON/MELAS overlap syndrome.
  
  
  
  We describe a unique presentation of LHON/MELAS overlap syndrome resulting from a m.13046T>C mutation in a 12-year-old girl. In patients with sudden vision loss in which three of the most prevalent LHON mitochondrial mutations have been ruled out, molecular genetic examination should be extended to other mtDNA-encoded subunits of MTND5 complex I. Furthermore, atypical clinical presentations must be considered, even in well-described phenotypes.
authors.affiliation: a Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine , Charles University in Prague and General University Hospital in Prague , Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Kolarova
authors.affiliation: b Laboratory of the Biology and Pathology of the Eye, Institute of Inherited Metabolic Disorders, First Faculty of Medicine , Charles University in Prague and General University Hospital in Prague , Czech Republic.|c Department of Ophthalmology, First Faculty of Medicine , Charles University in Prague and General University Hospital in Prague , Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Liskova
authors.affiliation: a Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine , Charles University in Prague and General University Hospital in Prague , Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Tesarova
authors.affiliation: a Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine , Charles University in Prague and General University Hospital in Prague , Czech Republic.
authors.forename: Vendula
authors.initials: V
authors.lastname: Kucerova Vidrova
authors.affiliation: d Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine , Charles University in Prague and General University Hospital in Prague , Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Forgac
authors.affiliation: e Department of Pathology and Molecular Medicine , Second Faculty of Medicine, Charles University in Prague and University Hospital Motol in Prague , Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Zamecnik
authors.affiliation: a Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine , Charles University in Prague and General University Hospital in Prague , Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Hansikova
authors.affiliation: a Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine , Charles University in Prague and General University Hospital in Prague , Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Honzik
mesh_terms: D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000235:genetics*; D005260:Female; D006801:Humans; D017241:MELAS Syndrome / Q000175:diagnosis / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014786:Vision Disorders / Q000175:diagnosis / Q000235:genetics; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; C481838:MT-ND5 protein, human; D042967:Electron Transport Complex I
keywords: LHON; MELAS; ND5; loss of vision; mitochondrial DNA; overlap syndrome