NeuroOp Guru: The role of muscle biopsy in heteroplasmy detection

This latest episode of the “NeuroOp Guru”—hosted by Andrew G. Lee, MD, from Houston Methodist, and joined by Drew Carey, MD, from Johns Hopkins University—features a retrospective study¹ on somatic mitochondrial mutations and their variable neuro-ophthalmic manifestations.

Mitochondrial diseases are typically inherited maternally, but mutations can also arise post-fertilization and affect specific tissues. These somatic mutations may present with mild symptoms like muscle manifestations or isolated optic neuropathy, without the full spectrum of mitochondrial disease features (eg, seizures or cardiac issues).

Traditionally, high heteroplasmy (a higher percentage of affected mitochondria) was thought to be necessary for symptoms to manifest, but this study challenges that view.

Even low heteroplasmy (less than 5%) may cause disease, particularly in tissues like the optic nerve or extraocular muscles, which might show higher heteroplasmy despite muscle biopsies showing low levels. The take-home message is that mitochondrial disease can present variably, and muscle biopsy should be considered if genetic testing is inconclusive, especially when muscle-based symptoms are predominant.

Reference

1. Carey AR, Miller NR, Cui H, et al. Myopathy and ophthalmologic abnormalities in association with multiple skeletal muscle mitochondrial DNA deletions. J Neuroophthalmol. 2024;44(2):247-252. doi:10.1097/WNO.0000000000001984