Hemodialysis in MNGIE transiently reduces serum and urine levels of thymidine and deoxyuridine, but not CSF levels and neurological function

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare, autosomal-recessive mitochondrial disorder caused by TYMP mutations presenting with a multisystemic, often lethal syndrome of progressive leukoencephalopathy, ophthalmoparesis, demyelinating neuropathy, cachexia and gastrointes...

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Bibliographic Details
Published in:	Orphanet journal of rare diseases 2017-08, Vol.12 (1), p.135-4, Article 135
Main Authors:	Röeben, Benjamin, Marquetand, Justus, Bender, Benjamin, Billing, Heiko, Haack, Tobias B, Sanchez-Albisua, Iciar, Schöls, Ludger, Blom, Henk J, Synofzik, Matthis
Format:	Article
Language:	eng
Subjects:	Adult Ataxia Cachexia Care and treatment Central nervous system Central Nervous System Diseases - etiology Central Nervous System Diseases - pathology Central Nervous System Diseases - therapy Cerebrospinal fluid Demyelination Deoxyuridine - blood Deoxyuridine - urine Development and progression Enzymes Haemodialysis Hemodialysis Hereditary diseases Humans Intestinal Pseudo-Obstruction - genetics Intestinal Pseudo-Obstruction - pathology Intestinal Pseudo-Obstruction - therapy Letter to the Editor Leukoencephalopathy Male Medical research Metabolites Mitochondria Mitochondrial DNA Mitochondrial Encephalomyopathies - genetics Mitochondrial Encephalomyopathies - pathology Mitochondrial Encephalomyopathies - therapy Mitochondriopathy MNGIE Mutation Neuropathy Peritoneal dialysis Rare Diseases Renal Dialysis Stem cells Studies Thymidine Thymidine - blood Thymidine - urine Thymidine Phosphorylase Thymidine phosphorylases Transplants & implants Urine
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Summary:	Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare, autosomal-recessive mitochondrial disorder caused by TYMP mutations presenting with a multisystemic, often lethal syndrome of progressive leukoencephalopathy, ophthalmoparesis, demyelinating neuropathy, cachexia and gastrointestinal dysmotility. Hemodialysis (HMD) has been suggested as a treatment to reduce accumulation of thymidine and deoxyuridine. However, all studies so far have failed to measure the toxic metabolites in cerebrospinal fluid (CSF), which is the crucial compartment for CNS damage.Our study is the first prospective, longitudinal investigation, exploiting detailed serial testing of predefined clinical and molecular outcome parameters (including serial CSF assessments) in a 29-year-old MNGIE patient undergoing 1 year of extensive HMD. We demonstrate that HMD only transiently restores increased serum and urine levels of thymidine and deoxyuridine, but fails to reduce CSF levels of the toxic metabolites and is ineffective to influence neurological function. These findings have direct important implications for clinical practice: They prevent a burdensome, long-term invasive, but ultimately probably ineffective procedure in future MNGIE patients.
ISSN:	1750-1172 1750-1172