Mitochondrial neurogastrointestinal encephalomyopathy: A nonrenal indication for peritoneal dialysis

Abstract

Mitochondrial neurogastrointestinal encephalomyopathy is a rare autosomal recessive disorder characterized by severe muscle wasting, gastrointestinal dysmotility, leukoencephalopathy, peripheral neuropathy, and ophthalmoplegia. The pathogenesis involves the accumulation of very high concentrations of nucleosides dThd and dUrd along with depletion of nucleotide dCTP. One of the treatment measures is the removal of nucleosides dThd and dUrd by hemodialysis and peritoneal dialysis. Only a few patient reports of dialysis as a measure to remove nucleosides had been reported.

Mitochondrial Neurogastrointestinal Encephalomyopathy: Into the Fourth Decade, What We Have Learned So Far

“…It is noteworthy that advancements in experimental therapies for MNGIE are mostly of recent development; indeed, the first published data collection of all patients treated with AHSCT dates back to 2015, sixteen years after the mutation was first identified (Halter et al, 2015). It is also important to note, that predominantly in eastern countries, the most dated therapeutic approach, more specifically peritoneal dialysis and haemodialysis, are still being used in the management of MNGIE (Sivadasan et al, 2016; Chandra et al, 2018). A number of experimental therapies are currently under development with the aim of rescuing the phenotype by restoring homeostatic thymidine phosphorylase activity and/or normalizing systemic deoxyribonucleoside accumulations.…”

Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment

“…CAPD involves the filling of the peritoneal cavity with a dialysis solution to encourage the diffusion of thymidine and 2’-deoxyuridine from the blood passing through the capillary network within the peritoneal membrane, and then after several hours of exchange, draining the dialysate containing the metabolites from the peritoneal cavity to waste [ Figure 2 ]. This approach has been reported for the treatment of four single cases, with patients receiving exchanges every 4-8 h, over periods of 22-36 months [ 74 , 87 – 89 ] . Although CAPD had no reported effects on the plasma biochemical imbalances, in one study, it was shown to remove approximately 100 μmol per day of thymidine and 2’-deoxyuridine from the peritoneal cavity [ 74 , 87 ] .…”

“…Safety issues associated with the administration of CAPD were catheter infections, mild peritonitis, dialysis fluid leakage and shoulder pain [ 74 , 89 ] . Other safety factors associated with this procedure, but were not reported in these four cases, are CAPD-associated peritonitis with or without bowel perforation [ 90 , 91 ] .…”