Mitochondrial neurogastointestinal encephalomyopathy (MNGIE) is a mitochondrial disease that primarily impacts the digestive and nervous systems. It is a rare disorder; between 550 and 600 affected individuals have been reported in published literature [1,2,9 ], but estimates suggest there could be thousands of MNGIE patients worldwide. 

The average age of diagnosis of MNGIE is 18 years, although it can appear as early as 5 months of age or as late as 48 years of age [3]. Prior to the diagnosis of MNGIE, most affected individuals have a history of gastrointestinal (GI) symptoms (such as abdominal pain or intermittent diarrhea), minor fatigability, and thin build [1]. The first signs of MNGIE vary, and the order of symptoms appearance is unpredictable. However, the disorder is always progressive. Due to the severity of the GI symptoms that develop, most affected individuals do not survive past the age of 40[3]. Those with late-onset MNGIE have a milder form of the disease[4] and may be an exception.

Current interventions for MNGIE focus on symptom management to improve an affected individual’s quality of life[1,2]. However, there are transplant therapies under investigation that have slowed MNGIE progression and improved symptoms in initial studies[2,5,6,7].

• limb weakness, numbness, and tingling (particularly in the hands and feet)
• droopy eyelids
• weakness of the eye muscles
• hearing loss

Other symptoms that have been occasionally associated with MNGIE include[3]:

• short stature
• hormonal abnormalities
• liver disease

If you loved one shows signs of MNGIE, their healthcare provider may perform the following to establish a diagnosis[1,2]:

• tests for reduced thymidine phosphorylase functioning such as:
  • genetic testing for TYMP pathogenic variants
  • a thymidine phosphorylase activity assay
  • measurements of thymidine and deoxyuridine levels in the plasma
• brain imaging to detect changes in the brain associated with MNGIE

• monitoring and treatment of swallowing difficulties and airways
• dromperidone for nausea and vomiting
• eating frequent snacks/meals to overcome early satiety
• feeding tubes or intravenous supplementation for nutritional support
• antibiotic therapy for infections caused by bacterial overgrowth in the intestines

Options for managing the other symptoms of MNGIE may include[1]:

• physical and occupational therapy for mobility
• drugs that can help manage nerve pain such as amitriptyline, nortriptyline, and gabapentin

Since MNGIE is an inherited disorder, genetic counseling and testing for TYMP pathogenic variant in members of the affected individual’s family may be recommended.

Blood stem cell (e.g., bone marrow) and liver transplants have been shown to slow progression of MNGIE and improve symptoms in early studies[2,5,6,7]. However, these therapies are still under investigation and in some cases may only be recommended for those diagnosed early due to significant risks to individuals with advanced disease[2,6].

Are there any clinical trials for MGNIE?

There are no active trials as of Fall 2023. We suggest you visit our Clinical Trials page – which also includes a Clinical Trials Finder Tool. We also highly encourage you to join our patient registry, mitoSHARE, where we are actively recruiting MNGIE families.

• Get Support
  Connect with our Support & Education Team online, via email at support@umdf.org or phone at (888) 900-6486.

• Check our clinical trials finder
  Use our Clinical Trials Finder tool to see if you qualify for any clinical trials.

• Join our patient registry, mitoSHARE
  We are actively recruiting MNGIE families to participate in our patient registry, mitoSHARE. Patient registries like mitoSHARE are an integral part in charting a course toward treatments and cures for MNGIE and other mitochondrial diseases. There are currently over 30 active mitochondrial disease studies, including a handful of clinical trials. Next generation patient registries like mitoSHARE are an integral part of expanding that number.

• Become an advocate
  Ask your representatives to prioritize mitochondrial disease research and support via the UMDF Advocacy Center. We’ll send regular action items where you – and your friends and family – can let Congress know we need their support. Click here to sign up.

• Join the conversation online
  – UMDF Social Media Support Groups: Facebook Support Group
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• Get involved
  Join the fight by giving your voice, generosity, time, or energy. Click here to see how you can help.

• Research & Funding: UMDF has provided more than $15 million in research funding to find treatments for diseases like MNGIE. UMDF advocacy has helped secure an additional $160 million in federal funding via the Department of Defense and National Institutes of Health.
• Data: Over two decades ago, UMDF pioneered patient registries for the mitochondrial disease community. Today, our next generation patient registry, mitoSHARE, is helping chart a path toward the treatment and eventual cure of mitochondrial diseases.
• Patient Support: Thousands of families just like you depend upon UMDF for support and education on diseases like MNGIE. Attendance at our support meetings annually tops 7,000, including disease specific support meetings for families.
• Clinician Support: To help educate clinicians on diseases like MNGIE, we feature monthly Bench to Bedside clinician seminars, host the annual Mitochondrial Medicine Symposium, support the Mitochondrial Care Network, and educate clinicians on our Mito U platform.

• The National Organization for Rare Disorders (NORD): Mitochondrial Neurogastrointestinal Encephalopathy
• The National Institutes of Health (NIH) National Library of Medicine: Mitochondrial neurogastrointestinal encephalopathy disease

1. Hirano M. Mitochondrial Neurogastrointestinal Encephalopathy Disease. 2005 Apr 22 [Updated 2016 Jan 14]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1179/

2. Hirano M, Carelli V, De Giorgio R. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network. J Inherit Metab Dis. 2021;44(2):376-387. doi:10.1002/jimd.12300

3. Garone C, Tadesse S, Hirano M. Clinical and genetic spectrum of mitochondrial neurogastrointestinal encephalomyopathy. Brain. 2011;134(Pt 11):3326-3332. doi:10.1093/brain/awr245

4. Martí R, Verschuuren JJ, Buchman A, et al. Late-onset MNGIE due to partial loss of thymidine phosphorylase activity. Ann Neurol. 2005;58(4):649-652. doi:10.1002/ana.20615

5. Halter JP, Michael W, Schüpbach M, et al. Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy. Brain. 2015;138(Pt 10):2847-2858. doi:10.1093/brain/awv226

6. Zaidman I, Elhasid R, Gefen A, et al. Hematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalopathy: A single-center experience underscoring the multiple factors involved in the prognosis. Pediatr Blood Cancer. 2021;68(5):e28926. doi:10.1002/pbc.2892

7. Kripps K, Nakayuenyongsuk W, Shayota BJ, et al. Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Mol Genet Metab. 2020;130(1):58-64. doi:10.1016/j.ymgme.2020.03.001

8. Nishino I, Spinazzola A, Hirano M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science. 1999;283(5402):689-692. doi:10.1126/science.283.5402.689

9. Redha N, Al-Sahlawi Z, Hasan H, Ghareeb S, Humaidan H. Meningoencephalitis in a novel mutation in MNGIE (mitochondrial neurogastrointestinal encephalomyopathy) ending a familial diagnostic odyssey: A case series report. Journal of Central Nervous System Disease. 2024;16. doi:10.1177/11795735241241423