BACKGROUND: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.