Mitochondrial neurogastrointestinal encephalomyopathy

Mitochondrial neurogastrointestinal encephalomyopathy, known as MNGIE syndrome, is a very rare autosomal recessive inherited multisystem disease that mainly affects the digestive and nervous systems. The disease can develop at any time during childhood or adulthood, but usually its main symptoms appear by the age of 20. So far, about 70 patients with this disease have been described worldwide.

Etiopathogenesis
The cause is a mutation in the TYMP gene (formerly known as ECGF1). This gene is responsible for making an enzyme called thymidine phosphorylase, which breaks down the nucleoside thymidine into smaller molecules, thereby regulating its amount in cells. Mutations in the TYMP gene reduce thymidine phosphorylase activity, resulting in increased cell concentrations. This results in an imbalance in the number of nucleotides required for mtDNA replication. As a result, mutations accumulate in the mtDNA and thus become very unstable. These genetic changes disrupt the normal function of mitochondria and result in impaired mitochondrial energy metabolism.

Clinical picture

 * Gastrointestinal system

Most patients with this disease suffer from gastrointestinal dysmotility, in which the muscles and nerves of the digestive tract do not move the digested food effectively. The result is a feeling of fullness even after eating a small amount of food, dysphagia, nausea and vomiting after eating, abdominal pain, diarrhea and pseudoobstruction. These difficulties lead to gradual weight loss and reduction of muscle mass (cachexia).


 * Nervous system

Manifestations of the nervous system are milder. These include tingling, stiffness and weakness of the limbs (peripheral neuropathy). Other neurological manifestations include eyelid ptosis, ophthalmoplegia and hearing loss. MRI shows leukoencephalopathy. _

Diagnostics
The diagnosis of MNGIE should be considered especially in patients with failure and intestinal motility disorders, who also develop neurological symptoms. The method of choice in diagnosis is to determine the level of thymidine in the blood, but for genetic counseling in the affected family, diagnostics at the enzymatic and molecular level is necessary.

Resources _ _ _ edit source ]

 * BURGETOVÁ, Andrea, Pavel JEŠINA and VANĚČKOVÁ MANUELA. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) - a case report of a rare disease with radiological findings. Czech Radiology [online] . 2010, vol. 64, vol. 4, pp. 295-300, also available from < http://kramerius.medvik.cz/search/nimg/IMG_FULL/uuid:14838850-69b8-11e3-93fe-d485646517a0#page=1 >.


 * Genetics Home Reference. Mitochondrial neurogastrointestinal encephalopathy disease Print All  [online]. Last revision 2008-06, [cited. 2016-04-23]. < https://ghr.nlm.nih.gov/condition/mitochondrial-neurogastrointestinal-encephalopathy-disease >.

Related Articles _ _ edit source ]

 * Mitochondrial diseases
 * Disorders of pyrimidine metabolism

External links _ _ edit source ]

 * Genetics home reference
 * Journal of Czech Physicians - MNGIE Syndrome

Category :


 * Pediatrics
 * Genetics
 * Pathobiochemistry