Article

Mitochondrial diseases (MIDs) are a large group of heterogeneous disorders due to
mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) genes, the
latter encoding proteins involved in mitochondrial function.
A multisystem
clinical picture that involves several organs, including both the peripheral and
central nervous systems, is a common presentation of MID. Movement disorders,
even isolated ones, are not rare. Cerebellar ataxia is common in myoclonic
epilepsy with ragged red fibers (MERFF) due to mutations in the mitochondrial
transfer RNA (tRNA) lysine gene, in Kearns-Sayre syndrome due to mtDNA deletions,
in sensory ataxic neuropathy with dysarthria and ophthalmoplegia (SANDO) due to
nuclear POLG1 gene mutations, and also in ARCA2, Friedreich's ataxia, SPG7, SCA28
and autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) due to
mutations in nuclear genes involved in mitochondrial morphology or function.
Myoclonus is a key feature of MERFF, but may also be encountered in mitochondrial
encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), ARCA2, POLG1
mutations and Leigh syndrome. Dystonia is common in Leigh syndrome (which may be
caused by 75 different genes) and in Leber hereditary ocular neuropathy (LHON)
plus disease, due to mutations in mtDNA genes that encode subunits of NADH
dehydrogenase, as well as in ARCA2, pantothenate kinase-associated
neurodegeneration (PKAN), mitochondrial membrane protein-associated
neurodegeneration (MPAN) and POLG1 mutations. Other movement disorders are rarer
(such as parkinsonism, tremor, chorea). Although parkinsonism is more frequent in
POLG1 mutations, and myoclonus in MERFF, most movement disorders are found either
isolated or combined in numerous MIDs. The presence of associated neurological
signs, whether central or peripheral, or of evocative magnetic resonance imaging
(MRI) abnormalities (striatal necrosis) should prompt a search for MID. In cases
of a particular clinical spectrum (LHON, MERFF, Kearns-Sayre, SANDO, SPG7, ARCA2,
ARSACS), a search for the most frequently implicated mutation(s) is recommended.
In other cases, muscle biopsies followed by metabolic and genetic studies may be
useful for arriving at a diagnosis.
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