Toggle Main Menu Toggle Search

Open Access padlockePrints

Clinical, Genetic, and Radiological Features of Extrapyramidal Movement Disorders in Mitochondrial Disease

Lookup NU author(s): Mika Martikainen, Dr Yi Ng, Professor Grainne Gorman, Dr Charlotte Alston, Dr Andrew Schaefer, Professor Patrick Chinnery, Professor David Burn, Professor Robert Taylor, Professor Bobby McFarlandORCiD, Emeritus Professor Doug Turnbull


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


IMPORTANCE Extrapyramidal movement disorders associated with mitochondrial disease are difficult to treat and can lead to considerable disability. Moreover, potential new treatment trials on the horizon highlight the importance of genotype-phenotype associations and deep phenotyping of the movement disorders related to mitochondrial disease.OBJECTIVE To describe the phenotype, genetic etiology, and investigation of extrapyramidal movement disorders in a large and well-defined mitochondrial disease cohort.DESIGN, SETTING, AND PARTICIPANTS An observational cohort study at a single national referral center. Among 678 patients (87% adults) followed up at the Newcastle mitochondrial disease specialized referral center between January 1, 2000, and January 31, 2015, 42 patients (12 pediatric, 30 adult) with genetic or biochemical evidence of mitochondrial disease and with 1 or more predefined extrapyramidal movement disorders (parkinsonism, dystonia, tremor, chorea, and restless legs syndrome) were included.MAIN OUTCOMES AND MEASURES We investigated the prevalence and genetic causes of dystonia and parkinsonism as well as radiological findings in the context of movement disorders in mitochondrial disease. All patients were interviewed and examined. All available medical notes and clinical, radiological, and genetic investigations were reviewed. RESULTS Forty-two patients (mean [SD] age, 37 [25] years; 38% female) with mitochondrial disease (12 pediatric [age range, 4-14 years], 30 adult [age range, 20-81 years]) with extrapyramidal movement disorders were identified. Dystonia manifested in 11 pediatric patients (92%), often in the context of Leigh syndrome; parkinsonism predominated in 13 adult patients (43%), among whom 5 (38%) harbored either dominant (n = 1) or recessive (n = 4) mutations in POLG. Eleven adult patients (37%) manifested with either generalized or multifocal dystonia related to mutations in mitochondrial DNA, among which the most common were the m.11778G>A mutation and mutations in MT-ATP6 (3 of 11 patients [27%] each). Bilateral basal ganglia lesions were the most common finding in brain magnetic resonance imaging, usually associated with generalized dystonia or Leigh syndrome.CONCLUSIONS AND RELEVANCE Dystonia, often associated with Leigh syndrome, was the most common extrapyramidal movement disorder among pediatric patients with mitochondrial disease. Parkinsonism was the most prevalent extrapyramidal movement disorder in adults and was commonly associated with POLG mutations; dystonia was predominantly associated with mitochondrial DNA mutations. These findings may help direct genetic screening in a busy neurology outpatient setting.

Publication metadata

Author(s): Martikainen MH, Ng YS, Gorman GS, Alston CL, Blakely EL, Schaefer AM, Chinnery PF, Burn DJ, Taylor RW, McFarland R, Turnbull DM

Publication type: Article

Publication status: Published

Journal: JAMA Neurology

Year: 2016

Volume: 73

Issue: 6

Pages: 668-674

Print publication date: 01/06/2016

Online publication date: 25/04/2016

Acceptance date: 02/02/2016

ISSN (print): 2168-6149

ISSN (electronic): 2168-6157

Publisher: American Medical Association


DOI: 10.1001/jamaneurol.2016.0355


Altmetrics provided by Altmetric


Funder referenceFunder name
Lily Foundation
Michael J. Fox Foundation
National Health Service Highly Specialised Commissioners
Wellcome Trust
Medical Research Council (MRC) Centre for Neuromuscular Diseases
National Institute for Health Research
National Institute for Health Research Biomedical Research Centre in Age and Age Related Diseases award
Newcastle University Centre for Ageing
Parkinson's UK
Sigrid Juselius Foundation
096919Z/11/ZWellcome Trust Centre for Mitochondrial Research
G000608-1MRC Centre for Neuromuscular Diseases
G016354/1Biotechnology and Biological Sciences Research Council from the MRC
G0601943MRC Centre for Translational Muscle Disease Research
G0800674MRC Centre for Translational Research in Neuromuscular Disease Mitochondrial Disease Patient Cohort
G906919Wellcome Trust Centre for Mitochondrial Research
MC_UP_1501/2MRC Mitochondrial Biology Unit
NIHR-HCS-D12-03-04National Institute for Health Research