Blueberry Muffin Sign: A Diagnostic Histochemical Clue in Mitochondrial Myopathy
4 affiliations
- 1DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Knoxville, USA
- 2Medicine, Royal College of Surgeons in Ireland - Bahrain, Busaiteen, BHR
- 3Internal Medicine, Qatar University, Doha, QAT
- 4Neurosciences, Hamad Medical Corporation, Doha, QAT
Abstract
Chronic progressive external ophthalmoplegia (CPEO) is a rare manifestation of mitochondrial myopathy, marked by slowly progressive bilateral ptosis and ophthalmoplegia that can mimic other ocular myopathies, often leading to delayed diagnosis. We report a 63-year-old female with a 24-year history of slowly progressive bilateral ptosis, ophthalmoplegia, and proximal muscle weakness. Laboratory investigations, brain and orbital magnetic resonance imaging, and extensive genetic testing were unrevealing, and she did not respond to empirical treatment for presumed myasthenia gravis. Muscle biopsy demonstrated ragged red fibers, increased succinate dehydrogenase (SDH) activity, and cytochrome c oxidase (COX)-deficient fibers appearing intensely blue on combined SDH/COX staining, a pattern the authors term the "Blueberry Muffin Sign." Electron microscopy confirmed paracrystalline "parking lot" inclusions, supporting a diagnosis of CPEO due to mitochondrial myopathy. The "Blueberry Muffin Sign" on combined COX-SDH histochemical staining represents a potentially useful diagnostic clue for mitochondrial myopathy that may facilitate earlier recognition of CPEO, particularly when genetic testing is inconclusive; validation in larger, genetically characterized cohorts is needed to establish its diagnostic specificity and reproducibility.
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BibTeX
@article{alhatou2026blueberry,
title = {{Blueberry Muffin Sign: A Diagnostic Histochemical Clue in Mitochondrial Myopathy}},
author = {Abraham Alhatou and Omar M Alhatou and Anwar I Joudeh and Mohammed Alhatou},
journal = {Cureus},
year = {2026},
month = sep,
doi = {10.7759/cureus.117236},
url = {https://europepmc.org/article/PMC/PMC13722136},
note = {CC BY},
}
RIS
TY - JOUR
TI - Blueberry Muffin Sign: A Diagnostic Histochemical Clue in Mitochondrial Myopathy
AU - Abraham Alhatou
AU - Omar M Alhatou
AU - Anwar I Joudeh
AU - Mohammed Alhatou
PY - 2026
DA - 2026/09/30
JO - Cureus
DO - 10.7759/cureus.117236
UR - https://europepmc.org/article/PMC/PMC13722136
AB - Chronic progressive external ophthalmoplegia (CPEO) is a rare manifestation of mitochondrial myopathy, marked by slowly progressive bilateral ptosis and ophthalmoplegia that can mimic other ocular myopathies, often leading to delayed diagnosis. We report a 63-year-old female with a 24-year history of slowly progressive bilateral ptosis, ophthalmoplegia, and proximal muscle weakness. Laboratory investigations, brain and orbital magnetic resonance imaging, and extensive genetic testing were unrevealing, and she did not respond to empirical treatment for presumed myasthenia gravis. Muscle biopsy demonstrated ragged red fibers, increased succinate dehydrogenase (SDH) activity, and cytochrome c oxidase (COX)-deficient fibers appearing intensely blue on combined SDH/COX staining, a pattern the authors term the "Blueberry Muffin Sign." Electron microscopy confirmed paracrystalline "parking lot" inclusions, supporting a diagnosis of CPEO due to mitochondrial myopathy. The "Blueberry Muffin Sign" on combined COX-SDH histochemical staining represents a potentially useful diagnostic clue for mitochondrial myopathy that may facilitate earlier recognition of CPEO, particularly when genetic testing is inconclusive; validation in larger, genetically characterized cohorts is needed to establish its diagnostic specificity and reproducibility.
SN - 2168-8184
ER -