Last weekend, researchers, clinicians and patient advocates from around the world came together in the Netherlands to tackle a big question:
“What exactly do we mean by ‘Primary Mitochondrial Disease’ (PMD)?”
Whilst you might be surprised to hear that professionals are still debating the technical definition of mitochondrial disease, the conversation reflects how much our understanding of the condition continues to evolve, driven by advances in genetics, technology and research.
Reaching a shared understanding of how we define primary mitochondrial disease is crucial because it shapes how people are diagnosed and how their disease is understood, as well as how they can access ongoing support and future treatments.
Who was involved in the meeting?
The meeting brought together experts from a range of specialities in mitochondrial disease in Europe and the US. This included clinicians, geneticists, researchers and industry representatives alongside patient representatives, including The Lily Foundation’s Head of Patient Programmes, Katie Waller.
The day opened with a session titled ‘The Voice of the Patients’, led by Katie herself in partnership with Serena Massucci, Chief Scientific Officer from Italian patient association Mitocon. Opening the meeting in this way reflects a growing recognition of the need to ground discussions in the lived experiences of patients and families.
‘The Voice of the Patients’: what families told us about mitochondrial disease
Responding to our request for contributions, the community shared detailed and often difficult experiences of trying to understand and live with mitochondrial disease. Across those responses, several themes came through, including the gap between receiving a diagnosis and truly understanding what that diagnosis means in practice.
Many people described being told they have mitochondrial disease without a clear explanation of what that means. Others had been misdiagnosed for many years before being given a confirmed diagnosis of mitochondrial disease. Some told us how they’d had to source information about the disease themselves, often without guidance or support.
Terminology was a consistent source of confusion, with some people given a genetic result, others a syndrome name, and sometimes both, used interchangeably. This made it difficult to understand how diagnoses relate to each other or how to explain them to others.
Uncertainty about the future also came through strongly, particularly where syndrome names led to assumptions about what might happen next, despite the variability of mitochondrial diseases.
Inheritance was another area where misunderstandings were common, with many told the condition is always passed down the maternal line, which isn’t always the case.
Finally, whilst peer support plays an important role in coping with mitochondrial diseases, the different terminology used to describe the condition can sometimes add to confusion rather than reduce it.
Whilst the insights shared were drawn from the Lily community in the UK, the themes themselves reflected experiences seen more widely across the mito landscape, including through Lily’s involvement with International Mito Patients (IMP).
Reflecting on the impact of her presentation, Katie said: “What really struck me was the audience’s reaction to the insights shared by members of our community. For some, the experiences we shared were really surprising, while for others it was a familiar picture, reflecting what they were already hearing from patients and families in their own clinics. It was really encouraging to see how carefully people listened to the insights that we shared, repeatedly referring back to the quotes and themes from our presentation during the discussions that followed.”
How experts worked towards a shared definition
Over the following two days, the group worked through a series of statements, discussing and voting on each one using a Delphi process, a structured way of refining ideas over multiple rounds to build consensus.
Although the Delphi process doesn’t allow patient advocates and industry professionals to influence the voting process, representatives Katie and Serena were actively consulted as discussions developed, showing the importance placed on hearing from patients throughout the process. Towards the end of the meeting, they were also asked to reflect on the proposed definition and how well it aligned with the needs of patients and families.
What experts agreed on before the meeting
There are some areas where there was strong agreement even before the in-person meeting.
Primary mitochondrial disease is understood to be:
- A genetic condition
- Caused by changes in mitochondrial DNA or nuclear DNA
- Affecting how mitochondria function, often linked to energy production
- Able to affect one or multiple organ systems
- Able to present at any age
There was also agreement that diagnosis should bring together genetic findings and clinical features, rather than relying on a single test.
Where there is still uncertainty
There were some areas where a lack of strong consensus meant it was necessary to discuss them in more detail.
One area of discussion was how broad the definition of mitochondrial disease should be. Mitochondria are involved in many processes, not just energy production, and some experts felt the definition needs to reflect this wider role.
Genetics adds further complexity. Some people have confirmed genetic changes but don’t show expected results on testing, while others may show mitochondrial dysfunction for different reasons.
Heteroplasmy was another important topic. Low levels of mitochondrial DNA changes are common and don’t on their own confirm a diagnosis – and there’s a recognised ‘grey area’ where interpretation is more uncertain.
There are also ongoing questions about how to describe people who are strongly suspected to have mitochondrial disease but don’t yet have genetic confirmation.
Why this matters
Mitochondrial disease is complex and can affect multiple systems in the body in very different ways. A clearer and more consistent definition has the potential to improve how mito is diagnosed and understood, and to make it easier for people to navigate their condition in everyday life.
What happens next
This meeting is one step in a longer process. The statements discussed and voted on over these two days will now be refined and shared with a much larger international group of experts. This wider group will have the opportunity to review and contribute, helping to build a broader consensus.
The aim is to reach an internationally agreed definition that will eventually be published and used to guide clinical practice and future work in mitochondrial disease.
What this means for patients
What’s encouraging is that work like this reflects how much our understanding of mitochondrial disease has developed over time, particularly with advances in genetics, technology and research.
As knowledge evolves, the way conditions are defined also needs to evolve alongside. A clearer and more consistent definition can help ensure that diagnosis, care and support are based on the best available understanding of the disease.
Follow the latest mitochondrial research updates
We’re incredibly grateful to everyone who shared their experiences and gave permission for their voices to be included in this research.
We’ll continue to follow this work and share updates as the definition evolves. We’ll also be working with the organisers to develop a lay summary of the final outputs, helping to ensure the findings are clear and accessible to the wider mito community.
You can explore more research updates and stay up to date with the latest developments in mitochondrial disease research here in our Research Zone.