Mitochondrial neurogastrointestinal encephalopathy syndrome

Información en español 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 mainly affects the digestive system and nervous system. Signs and symptoms most often begin by age 20 and worsen with time.^[1] 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 and result in early satiety, nausea, dysphagia, gastroesophageal reflux, vomiting after eating (postprandial emesis), episodic abdominal pain and/or distention, and diarrhea . Affected people may also have cachexia, dropped eyelids or weakness of other muscles of the eyes, peripheral neuropathy (manifesting as tingling, numbness, and pain (paresthesias) symmetric weakness, that mainly affect the lower extremities) 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. MNGIE is caused by variations (mutations) in the TYMP gene, important for allowing adequate levels of thymidine in the mitochondria. Inheritance is autosomal recessive.^[1]^[2]

Diagnosis is confirmed by detecting the TYMP gene variations or the increased levels of thymidine and deoxyuridine in blood. Treatment depends on the problems that present, and may include management of the swallowing difficulties and airway protection; specific medication for neuropathic symptoms and for nausea and vomiting. Other treatment may include nutritional support, antibiotics for intestinal bacterial overgrowth, special education and and physical therapy.^[2] It is recommended to avoid medication that interfere with mitochondrial function, such as valproate, phenytoin, chloramphenicol, linezolid, aminoglycosides, and tetracycline.^[3]

Last updated: 4/25/2018

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abdominal distention	Abdominal bloating Abdominal swelling Belly bloating Bloating [ more ]	0003270
Abdominal pain	Pain in stomach Stomach pain [ more ]	0002027
Atrophic muscularis propria		0025149
Cachexia	Wasting syndrome	0004326
Dysphagia	Poor swallowing Swallowing difficulties Swallowing difficulty [ more ]	0002015
External ophthalmoplegia		0000544
Gastroesophageal reflux	Acid reflux Acid reflux disease Heartburn [ more ]	0002020
Leukoencephalopathy		0002352
Nausea		0002018
Poor appetite	Decreased appetite	0004396
Sensorimotor neuropathy		0007141
Small intestinal dysmotility		0012850
Vomiting	Throwing up	0002013
30%-79% of people have these symptoms
Abnormality of the cerebral white matter		0002500
Abnormality of the extraocular muscles		0008049
Abnormality of the hand	Abnormal hands Hand anomalies Hand deformities [ more ]	0001155
Abnormality of the mitochondrion		0012103
Decreased motor nerve conduction velocity		0003431
Decreased number of large peripheral myelinated nerve fibers		0003387
Decreased sensory nerve conduction velocity		0003448
Demyelinating peripheral neuropathy		0007108
Diarrhea	Watery stool	0002014
Distal muscle weakness	Weakness of outermost muscles	0002460
Easy fatigability		0003388
Elevated hepatic transaminase	High liver enzymes	0002910
Foot dorsiflexor weakness	Foot drop	0009027
Hyperalaninemia	Increased blood alanine Increased serum alanine [ more ]	0003348
Increased CSF protein		0002922
Lactic acidosis	Increased lactate in body	0003128
Paresthesia	Pins and needles feeling Tingling [ more ]	0003401
Peripheral axonal neuropathy		0003477
Ptosis	Drooping upper eyelid	0000508
Ragged-red muscle fibers		0003200
Sensorineural hearing impairment		0000407
5%-29% of people have these symptoms
Abnormal cell morphology		0025461
Anemia	Low number of red blood cells or hemoglobin	0001903
Cirrhosis	Scar tissue replaces healthy tissue in the liver	0001394
Decreased muscle mass	Underdeveloped muscles	0003199
Hypergonadotropic hypogonadism		0000815
Hypogonadotrophic hypogonadism		0000044
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Macrovesicular hepatic steatosis		0001403
1%-4% of people have these symptoms
Dementia	Dementia, progressive Progressive dementia [ more ]	0000726
Percent of people who have these symptoms is not available through HPO
Areflexia	Absent tendon reflexes	0001284
Autosomal recessive inheritance		0000007
Constipation		0002019
Cytochrome C oxidase-negative muscle fibers		0003688
Death in early adulthood		0100613
Distal amyotrophy	Distal muscle wasting	0003693
Distal sensory impairment	Decreased sensation in extremities	0002936
Gastrointestinal dysmotility		0002579
Gastroparesis	Delayed gastric emptying	0002578
Hypointensity of cerebral white matter on MRI		0007103
Intermittent diarrhea		0002254
Intestinal perforation		0031368
Malabsorption	Intestinal malabsorption	0002024
Malnutrition		0004395
Mitochondrial myopathy		0003737
Multiple mitochondrial DNA deletions		0003689
Progressive	Worsens with time	0003676
Progressive external ophthalmoplegia		0000590
Slender build	Thin build	0001533
Subsarcolemmal accumulations of abnormally shaped mitochondria		0003548

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 12/1/2018

Do you have updated information on this disease? We want to hear from you.

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

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

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

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include similar disorders with phenotypes that overlap between MNGIE and MELAS, MERRF or progressive external ophthalmoplegia (PEO; see these terms), for example patients with prominent gastrointestinal symptoms and genetic alterations either in the mitochondrial DNA (such as the MT-TL1 or MT-TK genes with the m.3243A>G ``MELAS'' mutation or the m.8313G>A ``MERRF'' mutation) or in the nuclear POLG gene encoding DNA polymerase gamma (responsible for mitochondrial DNA replication and implicated in PEO). Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

Differential diagnoses include similar disorders with phenotypes that overlap between MNGIE and MELAS, MERRF or progressive external ophthalmoplegia (PEO; see these terms), for example patients with prominent gastrointestinal symptoms and genetic alterations either in the mitochondrial DNA (such as the MT-TL1 or MT-TK genes with the m.3243A>G ``MELAS'' mutation or the m.8313G>A ``MERRF'' mutation) or in the nuclear POLG gene encoding DNA polymerase gamma (responsible for mitochondrial DNA replication and implicated in PEO).

Visit the Orphanet disease page for more information.

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.
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.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s 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

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: 1-888-964-2001
Telephone: +1-414-964-1799
Fax: +1-414-964-7176
E-mail: iffgd@iffgd.org
Website: https://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

Organizations Providing General Support

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

Do you know of an organization? We want to hear from you.

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

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.
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

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.