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

Connor D. Dietz; Kaancan Deniz; Jamie C. Fong; Soonmee Cha; Katherine P. Rankin; Suzee E. Lee; Michael D. Geschwind; Charles C. Windon

doi:10.1038/s44400-026-00081-z

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

Journal article

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

Connor D. Dietz, Kaancan Deniz, Jamie C. Fong, Soonmee Cha, Katherine P. Rankin, Suzee E. Lee, Michael D. Geschwind and Charles C. Windon

npj Dementia, Vol.2(1), 25

01/01/2026

DOI: 10.1038/s44400-026-00081-z

PMID: 42058635

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Abstract

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.

Neurology

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Biomedical and Life Sciences

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Neurosciences

Details

Title: Subtitle: A single large-scale mitochondrial DNA deletion presenting as rapidly progressive dementia in a 35-year-old male
Creators: Connor D. Dietz - University of California, San Francisco
Kaancan Deniz - University of California, San Francisco
Jamie C. Fong - University of California, San Francisco
Soonmee Cha - University of California, San Francisco
Katherine P. Rankin - University of California, San Francisco
Suzee E. Lee - University of California, San Francisco
Michael D. Geschwind - University of California, San Francisco
Charles C. Windon - University of California, San Francisco
Resource Type: Journal article
Publication Details: npj Dementia, Vol.2(1), 25
DOI: 10.1038/s44400-026-00081-z
PMID: 42058635
ISSN: 3005-1940
eISSN: 3005-1940
Publisher: Nature Publishing Group UK
Grant note: P30 AG062422 / National Institute on Aging (https://doi.org/10.13039/100000049)
Language: English
Date published: 01/01/2026
Academic Unit: Neurology
Record Identifier: 9985182277202771

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