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Musumeci et al. J Transl Genet Genom 2020;4:221-37 Journal of Translational
DOI: 10.20517/jtgg.2020.22 Genetics and Genomics

Review Open Access

Spectrum of movement disorders in mitochondrial
diseases

Olimpia Musumeci, Rosaria Oteri, Antonio Toscano

Unit of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina,
Messina 95125, Italy.
Correspondence to: Dr. Olimpia Musumeci, Department of Clinical and Experimental Medicine, AOU Policlinico G. Martino,
UOC Neurologia e Malattie Neuromuscolari, via Consolare Valeria 1, Messina 95125, Italy. E-mail: omusumeci@unime.it
How to cite this article: Musumeci O, Oteri R, Toscano A. Spectrum of movement disorders in mitochondrial diseases. J Transl
Genet Genom 2020;4:221-37. http://dx.doi.org/10.20517/jtgg.2020.22
Received: 2 Mar 2020 First Decision: 7 Apr 2020 Revised: 1 May 2020 Accepted: 15 Jun 2020 Available online: 24 Jun 2020
Science Editor: Andrea L. Gropman Copy Editor: Cai-Hong Wang Production Editor: Tian Zhang

Abstract
Mitochondrial disorders (MD) include a large group of maternally inherited, autosomal dominant, or recessive
genetic syndromes caused by mitochondrial dysfunction. MD can be diagnosed at any age and many of them show
a multisystem presentation with variable combinations of symptoms. Given the important role of mitochondria
in neuronal homeostasis, neurological manifestations, including movement disorders, can accompany MD.
Movement disorders (MoD), either hypo- or hyperkinetic type, are reported in MD, but the real incidence and a
detailed characterization of these features are not addressed in population-based studies. Dystonia, usually in
the context of Leigh syndrome, is the main extrapyramidal movement disorder in pediatric MD patients; whereas
parkinsonism is the most prevalent hypokinetic disorder in adult MD patients. Ataxia is a common feature in MD,
in both the pediatric and adult MD populations. Other MoD, such as myoclonus, chorea, or tremor, may also occur
in MD. MoD manifest more frequently in the context of a complex phenotype but rarely can be isolated. From a
genetic point of view, MoD are described in patients with either mutations in mtDNA or in nuclear genes related
to mitochondria, and the same gene can be associated with different types of MoD. Recent studies demonstrate
that the dopaminergic nigrostriatal system is very vulnerable to mitochondrial dysfunction and defects of mtDNA
maintenance are frequently associated with a nigrostriatal degeneration, which may explain the pathophysiological
mechanism. Therapeutic interventions for MoD in MD do not differ from treatment options used for MoD with
different etiopathological background. Some forms benefit from specific treatments, e.g., primary Coenzyme Q10
deficiencies. Newer therapeutic strategies have been pursued which act on different mechanisms of mitochondrial
dysfunction, but clinical trials are warranted to improve the management of MD patients.

Keywords: Mitochondrial diseases, dystonia, tremor, parkinsonism, myoclonus, basal ganglia, mtDNA mutations,
multiple deletions

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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