Mitochondrial NeuroGastroIntestinal Encephalopathy (MNGIE)

What is MNGIE?

MNGIE, or mitochondrial neurogastrointestinal encephalopathy, is an ultra-rare genetic condition. Affecting around one in 1 million people, this form of mitochondrial disease primarily affects the digestive and nervous systems.

It’s variable in its severity, with some patients developing quite severe disease early in life, and others not developing symptoms until much later in life. Other complications can develop, and approximately 10% of all those affected may develop cognitive problems

What causes MNGIE?

Unlike many other mitochondrial diseases, MNGIE disease is caused by a problem with a specific enzyme, rather than a fault in the mitochondrial DNA. This enzyme, called thymidine phosphorylase, is produced by a gene called TYMP.

Under normal circumstances, this enzyme helps the body clear toxic waste products that are naturally produced by all our cells. In people with MNGIE, a fault in the TYMP gene means the enzyme doesn’t work properly.

As a result, toxic waste products aren’t cleared properly and begin to build up in the body. Over time, this causes a severe form of mitochondrial disease which particularly damages the gut and nervous system.

MNGIE is an autosomal recessive condition, meaning it only occurs if both parents carry the faulty gene.

What are the symptoms of MNGIE?

MNGIE syndrome affects multiple organs in the body, and symptoms can vary from person to person. Symptoms often begin in childhood but can go unnoticed for many years.

Common symptoms include:

• Gastrointestinal issues: Severe digestive problems caused by disruption to normal bowel function.
• Neurological symptoms: Weakness and nerve damage due to damage to the peripheral nervous system.
• Cognitive difficulties: These impact approximately 10% of those affected.

People with MNGIE don’t all experience the disease in the same way. Some individuals develop symptoms early in childhood or adolescence. These cases often progress more quickly and symptoms may be more severe earlier on.

Others develop symptoms later in adulthood. These individuals often have milder symptoms at first, and the disease may progress more slowly.

The difference in age of onset and severity is what doctors refer to when they talk about different phenotypes.

How do you get a diagnosis of MNGIE?

Because the symptoms of MNGIE can be similar to other digestive conditions such as Crohn’s disease or coeliac disease, specialist testing is essential to reach a confirmed diagnosis.

Diagnosis of mitochondrial neurogastrointestinal encephalopathy usually involves a combination of the following:

• Assessment by specialist mitochondrial teams.
• Blood tests to measure thymidine phosphorylase enzyme activity.
• Genetic testing to identify mutations in the TYMP gene.

Are there any treatments for MNGIE?

As with all forms of mitochondrial disease, there is currently no cure for MNGIE, and existing treatments focus on managing symptoms and improving quality of life rather than treating the underlying cause of the disease.

There are currently two potential long-term treatment options that aim to address the underlying cause of MNGIE:

• Bone marrow transplant.
• Liver transplant.

Both approaches aim to introduce healthy cells with normal thymidine phosphorylase enzyme activity. This may help the body clear toxic waste products more effectively, reducing further damage to the mitochondria.

These treatments are complex, have associated risks and aren’t suitable for everyone, but they do offer hope for a more long-term approach to managing the disease.

Is there any ongoing research into MNGIE?

There is active research into MNGIE taking place around the world. Scientists are currently investigating gene therapies, liver transplants and engineered enzyme replacement therapies to find safer, more effective long-term treatment options. While these approaches are still at the pre-clinical stage, it’s hoped that they will move into clinical trials over the next decade.

Plans are also in place to set up a global natural history study for MNGIE. This involves doctors collecting information from patients over time to better understand how the disease develops and progresses. This information is essential for comparing the natural course of the condition with the effects of new treatments and determining how effective they are.

What support is available for MNGIE patients?

Living with a rare condition like MNGIE can be isolating. Here at The Lily Foundation, we provide practical advice and emotional support for patients and families. From residential support weekends to private Facebook groups and virtual get-togethers, we currently support over 1500 patients and families affected by all forms of mitochondrial disease.

The NHS Highly Specialised Service for Mitochondrial Disorders, based in London, Newcastle and Oxford, provide expert care including diagnosis, symptom management and disease monitoring. Genetic counselling is also available via NHS services to help those affected understand inheritance patterns and future family planning options.

If you or someone you love has been diagnosed with MNGIE, head over to our mitochondrial disease Q & A page which should help answer some of the questions you may have. If you’d like to speak to someone about your mitochondrial disease diagnosis, please don’t hesitate to get in touch.