Mitochondrial Neurogastrointestinal Encephalopathy Disease

摘要: Clinical characteristics Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease is characterized by progressive gastrointestinal dysmotility (manifesting as early satiety, nausea, dysphagia, gastroesophageal reflux, postprandial emesis, episodic abdominal pain and/or distention, and diarrhea); cachexia; ptosis/ophthalmoplegia or ophthalmoparesis; leukoencephalopathy; demyelinating peripheral neuropathy paresthesias (tingling, numbness, pain) symmetric distal weakness more prominently affecting the lower extremities). The order in which manifestations appear unpredictable. Onset usually between first fifth decades; about 60% of individuals, symptoms begin before age 20 years. Diagnosis/testing clinical diagnosis MNGIE based on presence severe dysmotility, cachexia, ptosis, external ophthalmoplegia, sensorimotor neuropathy, asymptomatic leukoencephalopathy observed brain MRI, family history consistent with autosomal recessive inheritance. can be established a proband detection one following: (1) biallelic pathogenic variants TYMP (formerly known ECGF1); (2) markedly reduced levels thymidine phosphorylase enzyme activity; (3) elevated plasma concentrations deoxyuridine. Management Treatment manifestations: primarily supportive includes attention to swallowing difficulties airway protection; dromperidone for nausea vomiting; gastrostomy, parenteral feeding nutritional support; antibiotics intestinal bacterial overgrowth; amitriptyline, nortriptyline, gabapentin neuropathic symptoms; specialized schooling arrangements; physical occupational therapy. Prevention secondary complications: Attention abnormalities diverticulosis, respectively, may help prevent aspiration pneumonia ruptured diverticula. Agents/circumstances avoid: Drugs that interfere mitochondrial function should avoided; medications metabolized liver used caution. Genetic counseling inherited an manner. parents affected individual are obligate heterozygotes therefore carry mutated allele; asymptomatic. Unless has offspring either carrier, his/her will variant TYMP. Carrier testing at-risk members prenatal pregnancies at increased risk possible once known.