Mitochondrial neurogastrointestinal encephalopathy syndrome

Title

Other Names:

MNGIE; Myoneurogastrointestinal encephalopathy syndrome; MNGIE syndrome; MNGIE; Myoneurogastrointestinal encephalopathy syndrome; MNGIE syndrome; Oculogastrointestinal muscular dystrophy; OGIMD; Polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction; POLIP; Thymidine phosphorylase deficiency See More

Categories:

Congenital and Genetic Diseases; Digestive Diseases; Eye diseases; Congenital and Genetic Diseases; Digestive Diseases; Eye diseases; Metabolic disorders; Nervous System Diseases; RDCRN See More

Summary Summary

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) syndrome is a condition that particularly affects the digestive system and nervous system. Signs and symptoms of this condition most often begin by age 20 and worsen with time. Almost all people with MNGIE have gastrointestinal dysmotility, in which the muscles and nerves of the digestive system do not move food through the digestive tract efficiently. Affected individuals also experience peripheral neuropathy, droopy eyelids (ptosis), weakness of the muscles that control eye movement (ophthalmoplegia), and hearing loss. Leukoencephalopathy, which is the deterioration of a type of brain tissue known as white matter, is a hallmark of MNGIE; however it does not usually cause symptoms in people with this disorder. Mutations in the TYMP gene cause MNGIE, and this condition is inherited in an autosomal recessive pattern.^[1]

Last updated: 9/24/2014

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Areflexia	-
Autosomal recessive inheritance	-
Cachexia	-
Constipation	-
Death in early adulthood	-
Decreased activity of cytochrome C oxidase in muscle tissue	-
Distal amyotrophy	-
Distal muscle weakness	-
Distal sensory impairment	-
Gastrointestinal dysmotility	-
Gastroparesis	-
Hypointensity of cerebral white matter on MRI	-
Intermittent diarrhea	-
Lactic acidosis	-
Leukoencephalopathy	-
Malabsorption	-
Malnutrition	-
Mitochondrial myopathy	-
Multiple mitochondrial DNA deletions	-
Progressive	-
Progressive external ophthalmoplegia	-
Ptosis	-
Ragged-red muscle fibers	-
Sensorineural hearing impairment	-
Subsarcolemmal accumulations of abnormally shaped mitochondria	-
Vomiting	-

Last updated: 6/1/2017

Diagnosis Diagnosis

The clinical diagnosis of mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE) is based on the presence of severe gastrointestinal dysmotility (when the muscles and nerves of the digestive system do not move food through the digestive tract efficiently), cachexia (wasting away of muscle and fat tissue), ptosis, external ophthalmoplegia (weakness in the muscles that control eye movement), sensorimotor neuropathy, asymptomatic leukoencephalopathy (observed on brain MRI), and a family history consistent with autosomal recessive inheritance.^[2]

Direct evidence of MNGIE syndrome can be provided by one of the following:

A blood test showing an increase in plasma thymidine concentration (greater than 3 µmol/L) and an increase in plasma deoxyuridine concentration (greater than 5 µmol/L). This is sufficient to make the diagnosis of MNGIE disease.
Thymidine phosphorylase enzyme activity in leukocytes (white blood cells) less than 10% of the control mean.^[2]

Genetic testing of TYMP, the gene for thymidine phosphorylase (the enzyme deficient in individuals with MNGIE syndrome), detects mutations in approximately all of affected individuals.^[2]

Last updated: 6/6/2011

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment Treatment

Establishing the correct diagnosis of MNGIE disease may help avoid unnecessary exploratory abdominal surgeries, risks associated with anesthesia, and inappropriate therapies. Cooperation among multiple specialties including neurology, medical genetics, nutrition, gastroenterology, pain management, psychiatry, and physical/occupational therapy can help with earlier detection and treatment of the various aspects of multi-organ dysfunction that can occur in individuals with MNGIE syndrome. However, once symptoms appear, treatment is generally supportive.^[2]

Management of gastrointestinal (GI) dysfunction can include: early attention to swallowing difficulties and airway protection, especially in severely affected individuals; dromperidone for nausea and vomiting; celiac plexus or splanchnic nerve block to reduce abdominal pain; nutritional support such as bolus feedings, gastrostomy tube placement, and total parenteral nutrition; antibiotic therapy for intestinal bacterial overgrowth; and medication regimens that may include morphine, amitriptyline, gabapentin, and phenytoin for relief of neuropathic symptoms. Special schooling arrangements are often necessary. Physical therapy and occupational therapy may help preserve mobility.^[2]

It is generally recommended that individuals with MNGIE syndrome avoid drugs that interfere with mitochondrial function including valproate, phenytoin, chloramphenicol, tetracycline, and certain antipsychotic medications.^[2]

There are some therapies for MNGIE syndrome under investigation, such as attempting to normalize the concentrations of thymidine inside the cells to reduce the rate of the mitochondrial DNA damage, which progressively increases in an individual over time. Possible future treatments may include decreasing plasma thymidine concentration by reducing renal reabsorption of thymidine, by dialysis, and by enzyme replacement therapy (ERT).^[2]

Last updated: 6/6/2011

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Patient Registry

The North American Mitochondrial Disease Consortium (NAMDC) is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research. The North American Mitochondrial Disease Consortium (NAMDC) has a registry for patients who wish to be contacted about clinical research opportunities.

For more information on the registry see: http://rarediseasesnetwork.epi.usf.edu/registry/index.htm

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

American Gastroenterological Association
4930 Del Ray Avenue
Bethesda, MD 20814
Telephone: 301–654–2055
Fax: 301–654–5920
E-mail: communication@gastro.org
Website: http://www.gastro.org/patient
Association of Gastrointestinal Motility Disorders, Inc. (AGMD)
AGMD International Corporate Headquarters
12 Roberts Drive
Bedford, MA 01730
Telephone: 781-275-1300
E-mail: digestive.motility@gmail.com
Website: http://www.agmd-gimotility.org
Gastroparesis and Dysmotilities Association (GPDA)
5520 Dalhart Hill NW
Calgary, AB
T3A 1S9
Canada
Telephone: 403-247-3215
E-mail: jkf@gpda.net
Website: http://www.digestivedistress.com
International Foundation for Functional Gastrointestinal Disorders (IFFGD)
PO Box 170864
Milwaukee, WI 53217
Toll-free: 888-964-2001
Telephone: 414-964-1799
Fax: 414-964-7176
E-mail: iffgd@iffgd.org
Website: http://iffgd.org/
MitoAction
PO Box 51474
Boston, MA 02205
Toll-free: 888-648-6228
Telephone: 1-888-MITO-411 (648-6411) for support line
E-mail: info@mitoaction.org
Website: http://www.mitoaction.org
The Mitochondria Research and Medicine Society
PO Box 55322
BLSC Building, Room # 3-316
Elm and Carlton Streets
Birmingham, AL
Telephone: 716-907-4349
Fax: 716-845-1047
E-mail: contact@mitoresearch.org
Website: http://www.mitoresearch.org
United Leukodystrophy Foundation (ULF)
224 North Second Street
Suite 2
DeKalb, IL 60115
Toll-free: 800-728-5483
Telephone: 815-748-3211
Fax: 815-748-0844
E-mail: office@ulf.org
Website: http://www.ulf.org/
United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
Toll-free: 888-317-8633
Telephone: 412-793-8077
Fax: 412-793-6477
E-mail: info@umdf.org
Website: http://www.umdf.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Healthcare Resources

You can submit a question to Ask the Mito Doc^SM , a service of the United Mitochondrial Diseases Foundation. Information contained in Ask the Mito Doc^SM is for informational and educational purposes only.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Mitochondrial neurogastrointestinal encephalopathy syndrome. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Mitochondrial neurogastrointestinal encephalopathy syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

NCATS Co-Sponsored Conferences

Nutritional Interventions in Primary Mitochondrial Disorders: Developing an Evidence Base Tuesday, December 2, 2014 - Wednesday, December 3, 2014
Location: NIH Campus, Bethesda, MD
Description: The goal of this meeting is to explore the use of nutritional interventions, including dietary supplements, in primary mitochondrial disorders (PMD); identify gaps in knowledge; develop a research agenda; and identify research opportunities to promote an evidence base for the use of nutritional interventions in primary mitochondrial disorders.

Contact: Kathryn Camp, MS, RD, CSP,(301) 435-3608, campkm@od.nih.gov

Co-funding Institute(s): Office of Dietary Supplements, Office of Rare Diseases Research
2013 Neurobiology of Disease in Children Symposium: Mitochondrial Disease Wednesday, October 30, 2013 - Wednesday, October 30, 2013
Location: Austin, TX
Description: The topic for the 2013 NDC Symposium is Mitochondrial Disease. The NDC Symposium is a forum for preeminent investigators assembled to discuss recent accomplishments and future directions with a large group of child neurologists, program officers from the National Institutes of Health, and members of dedicated foundations and associations.

Contact:

Co-funding Institute(s): National Institute of Neurological Disorders and Stroke, Office of Rare Diseases Research
- Agenda ( - 38KB)

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My daughter has all of the symptoms of MNGIE. She had a muscle biopsy and it came back normal. The geneticist that she saw said further testing is not necessary; is this correct? What can I do to help manage all of her issues? See answer
My doctor thinks I may have MNGIE.What tests can be performed to diagnosis this condition? See answer

Have a question? Contact a GARD Information Specialist.

References References

Mitochondrial neurogastrointestinal encephalopathy disease. Genetics Home Reference. June 2008; http://ghr.nlm.nih.gov/condition=mitochondrialneurogastrointestinalencephalopathydisease. Accessed 9/24/2014.
John M Shoffner. Mitochondrial Neurogastrointestinal Encephalopathy Disease. GeneReviews. May 11, 2010; http://www.ncbi.nlm.nih.gov/books/NBK1179/. Accessed 3/27/2011.

Do you know of a review article? Send us your suggestions.