Neurogastrointestinal -MNGIE- Mitochondrial Encephalopathy (neurogastrointestinal Mitochondrial encephalopathy disease -MNGIE-) - Gen TYMP.
The neurogastrointestinal mitochondrial encephalopathy (MNGIE) is a disease that affects many parts of the body, particularly the gastrointestinal tract and nervous system. The main features of the MNGIE disease can appear at any time from infancy to adulthood, but more often the signs and symptoms begin around 20 years old and tend to worsen over time.
Digestive system abnormalities are some of the most frequent and severe features MNGIE disease. Almost all affected exhibit altered gastrointestinal motility, causing the muscles and nerves in the digestive system does not transport food through the digestive tract efficiently. As a result, those affected have full after eating only a small amount, dysphagia, nausea and vomiting after eating, episodes of abdominal pain, diarrhea and intestinal obstruction. These gastrointestinal problems cause extreme weight loss and cachexia. Referring to nervous system abnormalities, although these tend to be milder than gastrointestinal problems, affected individuals have peripheral neuropathy, ptosis, ophthalmoplegia and hearing loss. Leukoencephalopathy, is a hallmark of the disease MNGIE.
This process is due to mutations in the gene TYMP (formerly known as ECGF1), located on the long arm of chromosome 22 (22q13.33). This gene encodes thymidine phosphorylase enzyme. Thymidine phosphorylase thymidine converts deoxyribose into two smaller molecules 2-1-phosphate and thymine. This chemical reaction is an important decomposition of thymidine, which helps to regulate the concentration of nucleosides into cells step. Thymidine phosphorylase plays an important role in maintaining the proper amount of thymidine in mitochondria. Mitochondria use nucleosides, including thymidine, to form new molecules of mitochondrial DNA, as needed.
They have identified approximately 50 mutations in the gene TYMP in people with neurogastrointestinal mitochondrial encephalopathy (MNGIE). These genetic changes reduce or eliminate greatly the activity of thymidine phosphorylase. A deficiency of this enzyme increases the thymidine until very high concentrations in the body. Thymidine excess appears to be detrimental to the mtDNA, interrupting regular maintenance and repair. As a result, mutations can accumulate in mtDNA, causing it to become unstable. Moreover, mitochondria can also present a depletion of mtDNA. These genetic changes alter the normal function of mitochondria. Although mtDNA abnormalities underlying digestive and neurological problems MNGIE characteristic of the disease, it is not clear how defective mitochondria cause the specific characteristics of the disease.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with mitochondrial encephalopathy neurogastrointestinal (MNGIE), by complete PCR amplification of exons TYMP gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).