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Changing faces of mitochondrial disease: autosomal recessive POLG disease mimicking myasthenia gravis and progressive supranuclear palsy

Lookup NU author(s): Dr Andrew Schaefer, Kate Craig, Sila Hopton, Gavin Falkous, Professor Robert Taylor, Dr Naomi Warren



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


© 2022 Author(s). Published by BMJ. Background Mitochondrial disorders are known to cause diverse neurological phenotypes which cause a diagnostic challenge to most neurologists. Pathogenic polymerase gamma (POLG) variants have been described as a cause of chronic progressive external ophthalmoplegia, which manifests with ptosis, horizontal and vertical eye movement restriction and myopathy. Autosomal dominant progressive external ophthalmoplegia is rarely associated with Parkinsonism responsive to levodopa. Methods We report a case of a 58-year-old man who presented with an eye movement disorder then Parkinsonism who made his way through the myasthenia then the movement disorder clinic. Results A diagnostic right tibialis anterior biopsy revealed classical hallmarks of mitochondrial disease, and genetic testing identified compound heterozygous pathogenic gene variants in the POLG gene. The patient was diagnosed with autosomal recessive POLG disease. Conclusions It is important to maintain a high index of suspicion of pathogenic POLG variants in patients presenting with atypical Parkinsonism and ophthalmoplegia. Patients with POLG-related disease will usually have ptosis, and downgaze is typically preserved until late in the disease. Accurate diagnosis is essential for appropriate prognosis and genetic counselling.

Publication metadata

Author(s): Elwan M, Schaefer AM, Craig K, Hopton S, Falkous G, Blakely EL, Taylor RW, Warren N

Publication type: Article

Publication status: Published

Journal: BMJ Neurology Open

Year: 2022

Volume: 4

Issue: 2

Online publication date: 08/12/2022

Acceptance date: 22/11/2022

Date deposited: 05/01/2023

ISSN (electronic): 2632-6140

Publisher: BMJ Publishing Group


DOI: 10.1136/bmjno-2022-000352


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Funder referenceFunder name
203105/Z/16/ZWellcome Trust
e UK NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children
Lily Foundation
MR/S005021/1Medical Research Council (MRC)
Pathological Society
UK NIHR Biomedical Research Centre for Ageing and Age-related disease award, Newcastle upon Tyne Foundation Hospitals NHS Trust