Non-myeloablative bone marrow transplant and platelet infusion can transiently improve the clinical outcome of mitochondrial neurogastrointestinal encephalopathy: A case report

Anesthetic Management of a Child with Mitochondrial Neurogastrointestinal Encephalopathy

“…MNGIE is a rare autosomal recessive genetic disorder directly associated with a deficiency of thymidine phosphorylase (TP) [1–4]. MNGIE results from a mutation in the TYMP gene (ECGF 1 gene) that encodes for thymidine phosphorylase (TP).…”

“…This mutation results in a reduction or elimination of TP activity. TP breaks down thymidine and regulates the levels of thymidine and deoxyuridine in the body via negative feedback loop, so shortage of TP allows thymidine to build up [2–4]. Mitochondria use thymidine to build new molecules of mitochondrial DNA (mtDNA), so the excess of thymidine can result in mutations that damage the replication, maintenance, and repair of mtDNA.…”

“…Mitochondria use thymidine to build new molecules of mitochondrial DNA (mtDNA), so the excess of thymidine can result in mutations that damage the replication, maintenance, and repair of mtDNA. Patients with MNGIE have low levels of TP; therefore, toxic levels of thymidine and deoxyuridine are responsible for causing irreversible mitochondrial mutations in these patients [4]. These mutations can result in a decrease in ATP production via oxidative phosphorylation in the respiratory chain found in mitochondria, affecting tissues that have high energy demands including cardiac, nervous, and skeletal muscle tissue.…”

“…MNGIE patients are now being offered an option to undergo allogeneic hematopoietic stem cell transplantation (HSCT) [2–4]. Although this innovation is new and has only been used successfully in nine MNGIE patients, this treatment is yielding promising results as it aims to normalize thymidine phosphorylase (TP) levels [2, 6].…”

“…Although this innovation is new and has only been used successfully in nine MNGIE patients, this treatment is yielding promising results as it aims to normalize thymidine phosphorylase (TP) levels [2, 6]. Studies have shown that early HSCT treatment in these patients helps deter disease progression by reversing the toxic nucleoside levels of thymidine and deoxyuridine found in patients with this disorder [2–4]. While stem cell transplantation has not been found to reverse mitochondrial mutations or help with neurological symptoms, improved gastrointestinal relief has been noted with this treatment.…”