Mitochondrial neurogastrointestinal encephalopathy disease (MNGIE) affects the digestive and the nervous system of the body. Most of the affected people present a condition where the muscles and the nerves of the digestive system do not effectively move food through the tract. The digestive problems include intestinal blockage, nausea and feeling fullness after eating a small quantity of food. As the result, they can present extreme weight loss and reduced muscle mass. The symptoms can develop from infancy to adulthood, although it commonly occurs around the age of 20 which continues to deteriorate.
Causes
MNGIE develops as the result of a mutation in the gene identified as TYMP which produces an enzyme known as thymidine phosphorylase. The genetic mutation causes the reduced or eliminates the activity of this enzyme which breaks down a molecule known as thymidine into smaller molecules that regulate the level of nucleosides in the cells. As the result, the excess accumulation of thymidine is believed to damage the mitochondrial DNA. It can also disrupt the process of maintenance and repair of mitochondrial DNA causing its instability and their depletion. This can affect the normal function of mitochondria. MNGIE is inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell from the parents are defective. The parents of the affected individual are each a carrier of one copy of the defective gene and don’t necessarily present the symptoms associated with this condition.
Symptoms
MNGIE presents a variety of gastrointestinal and neurological symptoms. The main features of this syndrome are the dysfunction of the muscles of the gastrointestinal tract which fails to contract that normally pushes food through the digestive tract. The symptoms associated with the gastrointestinal problem include diarrhea, abdominal pain, feeling of early fullness, difficulty swallowing, nausea and vomiting. The gastrointestinal problem can cause complications such as bacterial overgrowth in the intestines and malabsorption. Hence they present weight loss, loss of tissue and muscle mass. The neurological symptoms include drooping of the upper eyelid (ptosis), restricted movements of the eyes, hearing loss and peripheral neuropathy. They also present the leukoencephalopathy which is the deterioration of a type of brain tissue called the white matter which is evident in the MRI scan.
Diagnosis
The diagnosis is based on a thorough clinical evaluation, identification of features associated with this condition and various specialized tests. The blood test indicates increased lactic acid and the MRI demonstrates asymptomatic leukoencephalopathy. The condition can be confirmed by checking the activity of TP enzyme, detecting the high levels of plasma levels of the nucleosides thymidine and deoxyuridine. The diagnosis can also be confirmed with the genetic testing that identifies the mutation responsible for causing this condition.
Treatment
The treatment is based on the specific symptoms evident in each case. Treatments can include medications for vomiting, nausea and nerve dysfunction. Pain affecting various organs of the gastrointestinal tract can be treated with a procedure that temporarily disrupts the nerve impulses. The nutritional supplement may be given through parenteral feedings or gastrostomy tube. In some cases, the affected individuals may benefit from occupational and physical therapy.
References
https://rarediseases.org/rare-diseases/mitochondrial-neurogastrointestinal-encephalopathy/
