Spectrum of movement disorders in mitochondrial diseases

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

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