Toggle Main Menu Toggle Search

Open Access padlockePrints

Risk of cardiac manifestations in adult mitochondrial disease caused by nuclear genetic defects

Lookup NU author(s): Dr Albert Lim, Dr Daniel Jones, Dr Matt Bates, Dr Andrew Schaefer, Dr John O'Sullivan, Catherine Feeney, Dr John Bourke, Emeritus Professor Doug Turnbull, Professor Grainne Gorman, Professor Bobby McFarlandORCiD, Dr Yi NgORCiD



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


© BMJ Publishing Group Limited 2021. Objective: Regular cardiac surveillance is advocated for patients with primary mitochondrial DNA disease. However, there is limited information to guide clinical practice in mitochondrial conditions caused by nuclear DNA defects. We sought to determine the frequency and spectrum of cardiac abnormalities identified in adult mitochondrial disease originated from the nuclear genome. Methods: Adult patients with a genetically confirmed mitochondrial disease were identified and followed up at the national clinical service for mitochondrial disease in Newcastle upon Tyne, UK (January 2009 to December 2018). Case notes, molecular genetics reports, laboratory data and cardiac investigations, including serial electrocardiograms and echocardiograms, were reviewed. Results: In this cohort-based observational study, we included 146 adult patients (92 women) (mean age 53.6±18.7 years, 95% CI 50.6 to 56.7) with a mean follow-up duration of 7.9±5.1 years (95% CI 7.0 to 8.8). Eleven different nuclear genotypes were identified: TWNK, POLG, RRM2B, OPA1, GFER, YARS2, TYMP, ETFDH, SDHA, TRIT1 and AGK. Cardiac abnormalities were detected in 14 patients (9.6%). Seven of these patients (4.8%) had early-onset cardiac manifestations: hypertrophic cardiomyopathy required cardiac transplantation (AGK; n=2/2), left ventricular (LV) hypertrophy and bifascicular heart block (GFER; n=2/3) and mild LV dysfunction (GFER; n=1/3, YARS2; n=1/2, TWNK; n=1/41). The remaining seven patients had acquired heart disease most likely related to conventional cardiovascular risk factors and presented later in life (14.6±12.8 vs 55.1±8.9 years, p<0.0001). Conclusions: Our findings demonstrate that the risk of cardiac involvement is genotype specific, suggesting that routine cardiac screening is not indicated for most adult patients with nuclear gene-related mitochondrial disease.

Publication metadata

Author(s): Lim AZ, Jones DM, Bates MGD, Schaefer AM, O'Sullivan J, Feeney C, Farrugia ME, Bourke JP, Turnbull DM, Gorman GS, McFarland R, Ng YS

Publication type: Article

Publication status: Published

Journal: Open Heart

Year: 2021

Volume: 8

Issue: 1

Online publication date: 01/04/2021

Acceptance date: 05/02/2021

Date deposited: 22/04/2021

ISSN (print): 2398-595X

ISSN (electronic): 2053-3624

Publisher: BMJ Publishing Group


DOI: 10.1136/openhrt-2020-001510


Altmetrics provided by Altmetric


Funder referenceFunder name
203105/Z/16/ZWellcome Trust