Mitochondrial neurogastrointestinal encephalomyopathy: A rare multisystem disorder of gastroenterologic relevance

Background: Metabolic diseases, the pathogenesis of which affects both the gastrointestinal tract and the central and peripheral nervous systems, can result in severe clinical syndromes. These rare diseases may be caused by enzyme defects, which lead to multisystem disorders due to their involvement in central metabolic pathways. A prime example is mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Objective: This overview describes the clinical picture, explains the pathogenesis in detail, and provides instructions for diagnosis and clinical management. Materials and methods: Against the background of a subtle biochemical and molecular itemization of MNGIE pathogenesis, we present and discuss the available literature. Moreover, a diagnostic guideline is constructed and therapeutic approaches are presented. Results and discussion: MNGIE is a rare multisystem disorder with predominant gastrointestinal involvement due to defects in mitochondrial function. Underlying the disease are mutations in the nuclear encoded thymidine phosphorylase (TP) gene (TYMP), with concomitant changes in the nucleotide pool and secondary mitochondrial gene alterations. In autosomal recessive inheritance the clinical presentation is characterized by ocular motility disorders, leukoencephalopathy, and variable gastrointestinal dysmotility. In addition to determination of TP activity in buffy coat leukocytes, biochemical analysis of the plasma nucleotide thymidine (dThd) and deoxyuridine (dUrd) provides diagnostic indications, as well as sequencing of the TYMP gene. MNGIE-specific therapeutic options aim at reduction of elevated toxic nucleotide levels and/or enzyme substitution for restoration of TP activity. © 2017, Springer Medizin Verlag GmbH.