A single large-scale mitochondrial DNA deletion presenting as rapidly progressive dementia in a 35-year-old male

Single large-scale mitochondrial DNA deletions (SLSMDs) are among the most common mitochondrial disorders. Adult-onset rapidly progressive dementia (RPD) due to an SLSMD has not previously been described. A 35-year-old male was referred to our clinic for assessment of RPD after developing rapidly progressive cognitive, behavioral, and motor symptoms over 14 months. Serial brain MRIs demonstrated progressive severe left temporal, moderate right temporal, and mild global brain parenchymal atrophy without T2-weighted or diffusion-weighted MRI abnormalities. Blood and cerebrospinal fluid testing showed elevated nonspecific markers of neurodegeneration (neurofilament light chain, 14-3-3γ, and neuron-specific enolase). After excluding common etiologies of RPD, mitochondrial genome sequencing revealed a novel de novo SLSMD (m.608_14511del). Brain magnetic resonance spectroscopy of the left thalamus demonstrated spectra suggestive of a lactate peak. This case demonstrates that SLSMDs can present with RPD as the primary clinical manifestation and should be considered in the differential diagnosis of RPD in young adults.