Primary mitochondrial myopathy (PMM)

Primary mitochondrial myopathy, often referred to as PMM, is an umbrella term for mitochondrial disease that mainly affects the muscles, leading to weakness, fatigue and reduced exercise tolerance. (In medicine, ‘myo’ means muscle and ‘path’ refers to disease.)

What is primary mitochondrial myopathy?

PMMs are a group of genetic mitochondrial muscle diseases that share similar features of muscle weakness and fatigue. These conditions are caused by faults in the genes that affect how mitochondria produce energy, leading to reduced strength and stamina in muscle cells.

Primary mitochondrial myopathies can appear in both children and adults. In some people it can mainly affect the muscles that control eye movement, while in others it causes more general muscle weakness throughout the body. Early-onset forms can progress more quickly and involve several systems, while later-onset forms tend to progress more slowly.

Mitochondrial myopathy syndromes

Several recognised mitochondrial syndromes fall within the PMM group, including:

• Chronic Progressive External Ophthalmoplegia (CPEO). This primary mitochondrial myopathy tends to come on in adulthood and mostly affects the eye muscles and the thighs and shoulders.
• Kearns-Sayre syndrome (KSS). This syndrome tends to come on in childhood and is similar to CPEO but can be more severe and is associated with other difficulties such as heart rhythm problems, visual issues and changes in brain scan.
• Mitochondrial DNA depletion and multiple deletion syndromes, such as TK2 deficiency (TK2d). This condition can develop in childhood (more severe) or adulthood (less severe).
• MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes). This condition can cause a wide variety of symptoms; in many individuals muscle weakness is the most prominent symptom.

Although these mitochondrial conditions can look different from one another, they’re all linked by their impact on muscle function and energy production.

What are the symptoms of primary mitochondrial disease?

Symptoms of PMM can differ from person to person and may appear at any age. The condition usually causes progressive muscle weakness, which can lead to difficulties with daily tasks and mobility.

Primary mitochondrial myopathy can affect the body in any of the following ways:

Muscles

• Weakness in the shoulders, hips, neck or limbs.
• Fatigue and muscle pain during or after activity.
• Muscle wasting or low muscle tone.
• Difficulty walking, climbing stairs or lifting objects.
• Swallowing or speech difficulties.

Eyes

• Droopy eyelids (ptosis).
• Difficulty moving the eyes (ophthalmoplegia) – this may cause double vision.

Breathing

• Breathlessness or tiredness caused by weak breathing muscles – this symptom is often worse when lying down (orthopnoea).

General

• Exercise intolerance (tiring easily).
• Muscle cramps or pain.
• Episodes of muscle breakdown (rhabdomyolysis) triggered by exertion.

Children with early-onset primary mitochondrial myopathies may also have:

• Low muscle tone (hypotonia).
• Feeding difficulties.
• Delayed or lost motor milestones.
• Weak reflexes.

Although primary mitochondrial myopathies can be severe in infancy and childhood, many adults live with milder forms of the condition and are able to manage their symptoms with appropriate care and support.

What causes primary mitochondrial myopathy?

A primary mitochondrial disease is caused by changes in genes that affect mitochondrial function. These changes interfere with the way mitochondria produce energy, which means muscles and other organs don’t get the power they need to work properly.

Because muscles are particularly energy-dependent, they’re often the first part of the body to be affected. This is why weakness and fatigue are such common symptoms of primary mitochondrial myopathies.

What are the complications of primary mitochondrial myopathy?

Confirming a diagnosis of PMM can take time because the symptoms overlap with other muscle and nerve conditions. A diagnosis is usually made through a combination of clinical assessments and laboratory tests.

These may include:

• Genetic testing using a blood or urine sample to identify changes in genes linked to mitochondrial disease.
• Muscle biopsy to look for signs of mitochondrial changes in muscle tissue – in some cases, especially adults, genetic testing from muscle tissue may be required.
• Blood tests to check for certain chemical markers that may indicate mitochondrial dysfunction.
• Physical examination and review of symptoms by a neuromuscular specialist.
• MRI or other imaging of muscles.

An early and accurate diagnosis is vital as it helps patients access the right support and may allow participation in clinical studies exploring new treatment approaches. A genetic diagnosis can also help a family know if the condition is likely to occur in other members.

Are there any treatments for primary mitochondrial myopathies?

As is the case with all forms of mitochondrial disease, there is currently no cure for PMM.

In recent years, several small‑molecule clinical trials have explored potential treatments for primary mitochondrial myopathies. While results have been mixed, with some early promising signals and other trials not meeting their primary endpoints, this growing body of research reflects increasing global commitment to developing effective therapies for people living with PMM.

In the absence of approved treatments, care currently focuses on managing symptoms, preserving mobility and improving quality of life through the support of a multidisciplinary healthcare team.

This team may include neurologists, physiotherapists, respiratory specialists, dietitians and genetic counsellors. Care may involve:

• Regular, gentle exercise under professional supervision.
• Respiratory support if breathing muscles are affected.
• Nutritional advice and swallowing support.
• Energy management and pacing techniques.

With the right care, many people with a primary mitochondrial myopathy can continue to live fulfilling and active lives.

What are the best supplements for managing primary mitochondrial myopathies?

Often, specialists will start newly diagnosed patients with a course of Co-Enzyme Q10 on a trial basis for a short period, usually around 3 months. If the patient or family feel they’ve noticed a benefit, this will be continued, with other vitamins and supplements trialled as needed.

Due to a lack of clinical trials, concrete evidence about the benefits of vitamins and supplements is limited and most reports are anecdotal. Patients must always consult with their healthcare professional before taking any type of supplement.

Representing the patient voice in PMM research

In November 2024, The Lily Foundation took part in the European Neuromuscular Centre (ENMC) meeting in the Netherlands, which brought together international experts to review current understanding of primary mitochondrial myopathies.

Our Head of Patient Programmes, Katie, represented the voice of mitochondrial disease patients and families at the meeting, helping to ensure that lived experience is recognised as a vital part of future research and care planning.

You can read more about Lily’s role in representing the patient community at the ENMC meeting.

What support is there for primary mitochondrial myopathy

In the UK, expert care is available for patients affected by mitochondrial myopathy through the NHS Highly Specialised Services for Mitochondrial Disorders, which provide diagnosis, management and genetic counselling for patients and families.

At The Lily Foundation, we understand that living with PMM can be challenging both physically and emotionally. We’re here to offer practical guidance, emotional support and patient advocacy to help families feel less alone.

Alongside this, we fund vital research to improve understanding of mitochondrial disease and to drive the discovery of new treatments for the future.

If you or someone you know has recently been diagnosed with a primary mitochondrial myopathy, why not head over to our mitochondrial disease Q&A section where you’ll find lots more information. Alternatively, contact our support team if you’d like to connect with others who understand what it’s like to live with PMM.