MNGIE: Mitochondrial Neurogastrointestinal Encephalopathy

Mitochondrial Neurogastrointestinal Encephalopathy, also known as MNGIE, is a rare mitochondrial condition where errors in the mitochondrial genome (the set of DNA contained in a cell’s mitochondria) build up over time in different tissues. Mitochondria are parts of a cell that help turn the energy we get from food into energy that the body can use. They are also important in communication between body parts and creating other materials the body needs. Mitochondrial conditions can cause a variety of signs and symptoms in many parts of the body, particularly those that use a lot of energy like muscles and the brain.

• MNGIE
• polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction
• POLIP
• oculogastrointestinal muscular dystrophy
• OGIMD
• mitochondrial myopathy with sensorimotor polyneuropathy, ophthalmoplegia, and pseudo-obstruction
• MEPOP

TYMP (formerly known as ECGF1)

• Autosomal recessive

MNGIE is an inherited genetic condition, meaning it is passed down in a family. People usually have two copies of the TYMP gene (formerly known as ECGF1), one inherited from each parent. MNGIE occurs when there are changes in both copies of the TYMP gene (autosomal recessive inheritance). Someone who has a change in only one copy of the TYMP gene is called a carrier, and they usually do not have any medical symptoms. If both parents are carriers, there is a 1 in 4 chance with each pregnancy that their child will have MNGIE. Both males and females can have MNGIE.

The exact frequency of MNGIE is not known. It is thought to be very rare. More than 120 people with clinical features of MNGIE have been described in the medical literature, though this condition may be underdiagnosed.

Both Male and Female

MNGIE can cause a range of signs and symptoms typically beginning before age 20 (though onset can range from 5-60 years).   The exact features, onset, and severity can vary widely among people with this condition, even among members of the same family. Always check with your provider if new symptoms appear or you are concerned. Signs and symptoms may include:

• GI concerns may include: vomiting, nausea, diarrhea, abdominal pain, a feeling of early fullness (premature satiety), stomach rumblings (borborygmi), difficulty swallowing (dysphagia), and small sac-like protrusions (diverticula) of the inner intestines
• GI complications may include:  bacterial overgrowth and/or failure of the intestines to absorb nutrients during digestion (malabsorption).
• This can lead to weight loss as well as loss of tissue and muscle mass (cachexia). People with MNGIE are typically extremely thin and some have short stature.
• Numbness, tingling, or pain in the arms and legs (sensory neuropathy)
• Muscle weakness
• Drooping of the upper eyelid (ptosis) and weakness of other muscles around the eye which can restrict movements (ophthalmoplegia)
• Loss of the myelin sheath that covers nerve fibers in the brain (leukoencephalopathy)  observed on imaging. This is usually not associated with symptoms.
• Hearing loss
• Changes in the electrical signals of the heart (cardiac conduction defects)

MNGIE can be diagnosed by:

• Measuring biochemical markers in blood like lactate and pyruvate
• GI studies depending on symptoms (both imaging and exploratory procedures)
• Brain studies and imaging looking for changes in the structure of the brain (MRI)
• Heart studies looking for rhythm changes (EKG)
• Nerve studies (nerve conduction velocity study/NCV) to look for nerve function
• Liver and kidney studies to assess how well they are working
• Performing a genetic test to look for changes in genes known to cause MNGIE

No

There is currently no FDA-approved therapy for MNGIE. Treatment and management of MNGIE are symptomatic and supportive. This may include:

• Traditional treatment of GI symptoms with antibiotics for bacterial overgrowth
• Careful monitoring of swallowing ability and airways
• Nutrition support
• Physical therapy and occupational therapy
• Traditional treatment of heart conditions
• Hearing aids or cochlear implants for hearing loss
• Avoidance of mitochondrial toxins like certain drugs, tobacco, and alcohol
• Mitochondrial supplements
• Special schooling arrangements

• Audiology
• Cardiology
• Gastroenterology
• Neurology
• Ophthalmology
• Physical and occupational therapy

• Mitochondrial neurogastrointestinal encephalopathy syndrome – The National Institutes of Health
• Mitochondrial Neurogastrointestinal Encephalopathy – National Organization for Rare Disorders
• Mitochondrial Neurogastrointestinal Encephalopathy Disease – GeneReviews
• What is Mitochondrial Neurogastrointestinal Encephalopathy? – ThinkGenetic, Inc

Connecting with others impacted by a rare disease allows for vital information to be shared about day-to-day life, prevents isolation, and gives hope. Please contact MitoAction for peer support opportunities at 888-MITO-411 or email mito411@mitoaction.org.

Other resources we recommend are:

• New Patient Kit for Mitochondrial Conditions
• Planning and Preparation
• Monthly Expert Series
• Energy in Action Podcast