Mitochondrial neurogastrointestinal encephalomyopathy treated with peritoneal dialysis and bone marrow transplantation

Abstract

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disease caused by thymidine phosphorylase deficiency which leads to toxic accumulations of thymidine (dThd) and deoxyuridine (dUrd). It lacks an established treatment and the prognosis is traditionally poor. We report a case of a young female patient with normal renal function and MNGIE treated by peritoneal dialysis (PD) and allogeneic bone marrow transplantation (BMT). PD was effective in reducing dThd and dUrd plasma levels and in improving clinical symptoms. To our knowledge, this is the first report on the beneficial effects of PD regarding MNGIE neurological symptoms. PD, therefore, should be considered especially in medically compromised patients as a supportive treatment to improve clinical conditions before BMT.

Mitochondrial neurogastrointestinal encephalomyopathy: A nonrenal indication for peritoneal dialysis

“…In another report, the PD was continued for 15 months. [ 13 ] An improvement in gastrointestinal symptoms and mitigation of numbness in hands and legs observed; eventually, the patient underwent heterologous HSCT.…”

Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment

“…Clinical improvements were reported in all four patients and included reductions in vomiting, nausea and epigastric pain; no longer requiring parenteral nutrition; improvements in appetite; increases in body weight (ranging between 3.5 and 13 kg); slight improvement in sensorimotor polyneuropathy and sensory ataxia; and a resolution of the numbness in peripheries. Regained abilities to perform normal daily activities were also reported, for example climb stairs, ambulant without support and improved walking distances [74,87,88] . Of interest, many of the clinical improvements reported were gastrointestinal in nature, and CAPD may therefore offer an important approach to targeting the gastrointestinal symptoms of MNGIE.…”

“…The rationale of the approach is based on the diffusion of plasma thymidine and 2'-deoxyuridine across the membrane of donor platelets via nucleoside transports into the cells where they are metabolised by the cytosolic-based thymidine phosphorylase into their normal products, thymine and uracil, respectively. Four cases are reported in the literature using this procedure [87,93,94] . Reductions in plasma deoxyribonucleoside concentrations, equating to 50%-70% of baseline concentrations, were reported in one patient who received three platelet infusions on Days 0, 4 and 7, with thymidine phosphorylase activity peaking 24 h after each infusion.…”

Mitochondrial Neurogastrointestinal Encephalomyopathy Caused by Thymidine Phosphorylase Enzyme Deficiency: From Pathogenesis to Emerging Therapeutic Options

“…A MNGIE patient who had peritoneal dialysis showed an improvement in gastrointestinal symptoms (such as vomiting, anorexia, abdominal pain, and diarrhea) during the continuing peritoneal dialysis for 3 years with body weight gain, although other major symptoms including ocular and neurological abnormalities and brain MRI signals did not change ( Yavuz et al, 2007 ). Another case report noted improvement of the gastrointestinal and neurological symptoms, mainly the mitigation of numbness in the hands, until nucleoside levels increased again 15 months after continuous ambulatory peritoneal dialysis ( Ariaudo et al, 2014 ).…”