Rare Nephrology News

Disease Profile

Mitochondrial neurogastrointestinal encephalopathy syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

1-9 / 1 000 000

US Estimated

Europe Estimated

Age of onset

Adolescent

ICD-10

G71.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

MNGIE; Myoneurogastrointestinal encephalopathy syndrome; MNGIE syndrome;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Eye diseases;

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]

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.

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
Paralysis or weakness of muscles within or surrounding outer part of eye
0000544
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

 0002020
Leukoencephalopathy
0002352
Nausea
0002018
Poor appetite
Decreased appetite
0004396
Sensorimotor neuropathy
Nerve damage causing decreased feeling and movement
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
0003199
Hypergonadotropic hypogonadism
0000815
Hypogonadotropic 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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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]

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

    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 multiorgan 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]

    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

      Organizations Providing General Support

        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

        • MedlinePlus Genetics 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.

            References

            1. Mitochondrial neurogastrointestinal encephalopathy disease. Genetics Home Reference. June 2008; https://ghr.nlm.nih.gov/condition=mitochondrialneurogastrointestinalencephalopathydisease.
            2. Hirano M. Mitochondrial Neurogastrointestinal Encephalopathy Disease. GeneReviews. 2016; https://www.ncbi.nlm.nih.gov/books/NBK1179/.
            3. Mitochondrial neurogastrointestinal encephalopathy disease. National Organization for Rare Diseases (NORD). 2012; https://rarediseases.org/rare-diseases/mitochondrial-neurogastrointestinal-encephalopathy/.

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