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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. 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.
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. It is recommended to avoid medication that interfere with mitochondrial function, such as valproate, phenytoin, chloramphenicol, linezolid, aminoglycosides, and tetracycline.
Source: GARD Last updated on 05-01-20
MNGIE can be diagnosed by measuring concentrations of thymidine and deoxyuridine in the blood. Elevated levels of plasma thymidine and deoxyuridine are sufficient to make the diagnosis. In addition, the activity of an enzyme called thymidine phosphorylase can be measured in white blood cells (leukocytes). If the activity of this enzyme is less than 10 percent of normal, the diagnosis of MNGIE is confirmed.
Genetic testing can also be performed for MNGIE, and it is typically used to identify unaffected carriers of the condition. First, a DNA sample from an affected individual is tested to identify a change (mutation) in the TYMP gene (also called ECGF1). This gene provides instruction for making the thymidine phoshorylase enzyme. Once a mutation in identified, unaffected family members can undergo genetic testing for that specific mutation.
GeneTests lists the names of laboratories that are performing clinical testing for MNGIE.
Please note: Most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.
Last updated on 05-01-20
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.
Direct evidence of MNGIE syndrome can be provided by one of the following:
Last updated on 05-01-20
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.
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.
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.
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).
Last updated on 05-01-20
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