Mitochondrial Donation in a Reproductive Care Pathway for mtDNA Disease

McFarland, Robert Ph.D.
Hyslop, Louise A. Ph.D.
Feeney, Catherine M.Sc.
Pillai, Rekha N. Ph.D.
Blakely, Emma L. Ph.D.
Moody, Eilis M.Sc.
Prior, Matthew Ph.D.
Devlin, Anita M.D.
Taylor, Robert W. D.Sc.
Herbert, Mary Ph.D.
Choudhary, Meenakshi Ph.D.
Stewart, Jane A. M.D.
Turnbull, Douglass M. Ph.D.

¹Mitochondrial Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
²NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
³Newcastle Fertility Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, International Centre for Life, Newcastle upon Tyne, United Kingdom
⁴Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
⁵Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
⁶Biosciences Institute, Newcastle University, Biomedicine West Wing, Centre for Life, Newcastle upon Tyne, United Kingdom
⁷Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia

Dr. Turnbull can be contacted at [email protected]. Dr. McFarland can be contacted at [email protected].

The Highly Specialised Mitochondrial Reproductive Care Pathway is supported by the NHS at Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. Support was provided by Wellcome (203105/Z/16/Z and 206001/Z/16/Z). Infrastructural support was provided by Newcastle University; a National Institute for Health and Care Research Biomedical Research Centre award to the Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; and the NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on July 16, 2025, at NEJM.org.

We thank Alex Bright, Carol Shaw, Jan Dutton, Corina Moldova, Neil Seller, Satish Adwani, Ed Blair, Rachel Oliver, Bernadette Brent, Ruth Curry, and Fredrik Karpe for their help in managing patients; Lyndsey Butterworth for public engagement in developing the reproductive pathway; and the clinical and laboratory staff of the NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children and the Newcastle Fertility Centre at the International Centre for Life.

New England Journal of Medicine 393(5):p 461-468, July 31, 2025. | DOI: 10.1056/NEJMoa2503658

Summary

Pathogenic variants in mitochondrial DNA (mtDNA) are a common cause of severe, often fatal, inherited metabolic disease. A reproductive care pathway was implemented to provide women carrying pathogenic mtDNA variants with reproductive options. A total of 22 women with pathogenic mtDNA variants have commenced or completed pronuclear transfer (and thus receipt of a mitochondrial donation), and there have been 8 live births. All 8 children were healthy at birth, with no or low levels of mtDNA heteroplasmy in blood. Hyperlipidemia and cardiac arrhythmia developed in a child whose mother had hyperlipidemia during pregnancy; both of the child's conditions responded to treatment. Infant myoclonic epilepsy developed in another child, with spontaneous remission. At the time of this report, all the children have made normal developmental progress. (Funded by the U.K. National Health Service and others.)