Neuropsychiatry Journal

Letter To The Editor

Movement disorders and cerebellar involvement in mitochondrial disorders

OA J Neuropsychiatr.
© Finsterer J et al
Received: 06-March-2018
Accepted: 07-May-2018
Published: 21-May-2018
Peer Review Reports

Letter to the Editor

Recently, a paper about 50 patients with a genetically confirmed mitochondrial disorder (MID) who also presented with different types of movement disorders had been published by Schreglmann et al. [1]. We want to express some concerns and add some comments about this study.

MIDs not only manifest with movement disorders such as parkinsonism, dystonia, chorea, myoclonus, or ataxia, but also with athetosis, restless-leg syndrome, tics and Tourette syndrome, or tremor [2]. Athetosis has been particularly described in patients carrying mutations in the WARS2, C10orf2 (manifesting as infantile onset spinocerebellar ataxia), and ACO2 genes and in patients with Leigh syndrome. Restless-leg syndrome has been only occasionally reported as a manifestation of a MID. In a Gypsy female with mitochondrial multiorgan disorder syndrome (MIMODS), restless-leg syndrome was one among the multiple phenotypic features of the MID [3]. Restless-leg syndrome has been also found in a study of movement disorders in 678 MID patients from the UK [4]. In a study of 20 patients with genetically confirmed progressive external ophthalmoplegia, restless-leg syndrome, leading to sleep disturbance, was found in 35% of them. Tourette syndrome has been recently described in association with mutations in the nuclear-encoded mitochondrial genes MRPL3, DNAJC13, and OFCC1 respectively. Tics were one of the phenotypic manifestations of the m.3243A>G variant in an 11yo female with epilepsy and diabetes. Tremor in the absence of other Parkinsonian features has been repeatedly reported in MIDs. Tremor is usually a non-dominant feature in MIMODS and associated with mutations in genes encoding for tRNAs, COX15, or DGAT2. The latter patient manifested additionally with Charcot-Marie-Tooth disease. Thus, we would like to know if the authors are aware of MID patients presenting with movement disorders other than the ones reported and if these MID patients were tested for mutations in genes mentioned above.

Multiple mtDNA deletions or mtDNA depletion may not only be associated with mutations in POLG1, POLG2, C10orf2 (TWNK), and SLC25A4, but also in the TFAM, RNASEH1, MGME1, DNA2, TK2, DGUOK, SUCLG1, SUCLA2, ABAT, RRM2B, TYMP, AGK, MPV17, OPA1, MFN2, and FBXL4 genes [5]. Which was the reason why these other nuclear genes were not tested for mutations in patients with multiple mtDNA deletions?

Cerebellar atrophy is not an unusual finding in MIDs. It is often associated with atrophy of the brainstem. Specific and non-specific MIDs may go along with cerebellar atrophy. In some patients with a MID, cerebellar atrophy may be the dominant feature, whereas in other patients cerebellar atrophy may be a non-dominant feature of the phenotype. MIDs with dominant cerebellar atrophy include pontocerebellar hypoplasia type-6 and leukoencephalopathy with brainstem and spinal cord involvement and lactic acidosis [6]. Cerebellar atrophy as a non-dominant feature is caused by mutations in tRNA, rRNA, AIFM1, MRPS22, ATAD3, ADCK3, COQ4, GFM2, RARS2, TTC19, and TWNK genes respectively.

In summary, this interesting study could be more meaningful by discussing other types of movement disorders than the ones presented in association with MIDs, by testing patients with multiple mtDNA deletions for mutations in additional genes, and by a broader discussion of cerebellar atrophy in MIDs.


Mitochondrial, Hereditary neuropathy, Phenotype, Genotype, multisystem disease, Lactic acidosis


©2018 Josef Finsterer et al.; licensee OA Journal of Neuropsychiatry. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://


1. Schreglmann SR, Riederer F, Galovic M, et al. (2018) Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum. Mov Disord 33: 146-155.
2. Ghaoui R, Sue CM (2018) Movement disorders in mitochondrial disease. J Neurol 265: 1230-1240.
3. Finsterer J, Enzelsberger B, Bastowansky A (2017) Basal Ganglia Calcification with Tetanic Seizure Suggest Mitochondrial Disorder. Am J Case Rep 18: 375-380.
4. Martikainen MH, Ng YS, Gorman GS, et al. (2016) Clinical, Genetic, and Radiological Features of Extrapyramidal Movement Disorders in Mitochondrial Disease. JAMA Neurol 73: 668-674.
5. El-Hattab AW, Craigen WJ, Scaglia F (2017) Mitochondrial DNA maintenance defects. Biochim Biophys Acta 1863: 1539-1555.
6. Van der Knaap MS, Salomons GS (2010) Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation. 2015, University of Washington, Seattle.

Krankenanstalt Rudolfstiftung, Vienna, Austria

Discipline of Neuroscience. Escola Paulista de Medicina, São Paulo, Brazil

Departamento de Speech-Language Pathology. Escola Paulista de Medicina / Federal University of São Paulo, São Paulo, Brazil

Discipline of Neuroscience. Escola Paulista de Medicina, São Paulo, Brazil