Science News: Mitochondrial Disease in Adults: Recent Advances and Future Promise

Published April 18, 2022

Education Science News

Submitted by: Raymond Rosales, MD, PhD
Edited by: Francisco Gomez, MD

Ng YS, Bindoff LA, Gorman GS, et al. Mitochondrial disease in adults: Recent advances and future promise. Lancet Neurol. 2021;20(7):573-584. doi:10.1016/S1474-4422(21)00098-3

Summary: This article provides a thorough review of mitochondrial disorders in adults, including phenotype, imaging, genotype, and biomarkers.
Approximately two thirds of cases of adult-onset disease are caused by pathogenic mtDNA variants; the rest by nuclear DNA genomics. Newly discovered biomarkers include FGF2133 and GDF15, which are sensitive and specific for adult mitochondrial diseases but may not be widely available yet.
Features that can alert the clinician to mitochondrial myopathies include fatigability, myalgias (often exercise induced), exercise intolerance, and lactic acidemia. Some mitochondrial diseases might have concomitant peripheral neuropathy, be it axonal or demyelinating, including POLG-related disease and mitochondrial neurogastrointestinal encephalomyopathy. Mild bulbar weakness is not uncommon.
Chronic progressive external ophthalmoplegia (CPEO) is one of the most common adult clinical presentations of mitochondrial disease. Seronegative myasthenia gravis (MG) (without AchR and MuSK antibodies) is a notable differential diagnosis. Furthermore, patients with CPEO may present with minor neuromuscular junction electrophysiological abnormalities. Other differential diagnoses include oculopharyngeal muscular dystrophy, congenital MG syndrome, congenital myopathy, and myotonic dystrophy.
Other acute and subacute neurological presentations in mitochondrial disease include stroke-like episodes, new onset epilepsy, and brainstem findings secondary to metabolic processes. Subacute optic neuropathy and hearing loss may also be encountered.
The article includes an algorithmic approach to diagnosis of said diseases.
Comments: This article provides an up-to-date review of the clinical and biochemical approach to mitochondrial disorders in adults. The clinical approach algorithm is especially useful. The neuromuscular neuro-imaging features will hopefully also help clinicians.
This review will help everyone in the field understand the intricacies of mitochondrial disorders in adults.
The algorithm is useful for:

  • Suspected acute presentations of mitochondrial disease in adults: Stroke-like, brainstem and optic neuropathy.
  • Suspected slowly progressive neurological presentations of mitochondrial disease in adults: Myopathy or exercise intolerance, neuropathy, progressive optic neuropathy, and Ataxia with other systemic features
Articles of Similar Interest:
Gorman GS, Chinnery PF, DiMauro S, et al. Mitochondrial diseases. Nat Rev Dis Primers. 2016;2: 16080.
Ng YS, Bindoff LA, Gorman GS, et al. Consensus-based statements for the management of mitochondrial stroke-like episodes. Wellcome Open Res 2019;4:201.