title: Mitochondrial neurogastrointestinal encephalomyopathy in three siblings: clinical, genetic and neuroradiological features.
abstract: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder in which a nuclear mutation of the thymidine phosphorylase (TP) gene causes mitochondrial genomic dysfunction. Patients suffer from gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoparesis, myopathy and polyneuropathy. Magnetic resonance imaging (MRI) shows leukoencephalopathy. We describe clinical, genetic and neuroradiological features of three brothers affected with MNGIE. Clinical examination, laboratory analyses, MRI and magnetic resonance spectroscopy (MRS) of the brain, and genetic analysis have been performed in all six members of the family with the three patients with MNGIE. Two of them are monozygous twins. They all suffered from gastrointestinal dysmotility, cachexia, ophthalmoplegia, muscular atrophies, and polyneuropathy. Urinary thymidine was elevated in the patients related to the severity of clinical disease, and urinary thymidine (normally not detectable) was also found in a heterozygous carrier. Brain MRI showed leukoencephalopathy in all patients; however, their cognitive functioning was normal. Brain MRS demonstrated reduced N-acetylaspartate and choline in severely affected areas. MRI of heterozygous carriers was normal. A new mutation (T92N) in the TP gene was identified. Urinary thymidine is for the first time reported to be detectable in a heterozygous carrier. MRS findings indicate loss of neurons, axons, and glial cells in patients with MNGIE, but not in heterozygous carriers.
authors.affiliation: Department of Neurology, University Hospital-Inselspital, 3010 Bern, Switzerland.
authors.forename: W M M
authors.initials: WM
authors.lastname: Schüpbach
authors.forename: K Madhavi
authors.initials: KM
authors.lastname: Vadday
authors.forename: A
authors.initials: A
authors.lastname: Schaller
authors.forename: C
authors.initials: C
authors.lastname: Brekenfeld
authors.forename: L
authors.initials: L
authors.lastname: Kappeler
authors.forename: J F
authors.initials: JF
authors.lastname: Benoist
authors.forename: C Nguyen-Thi
authors.initials: CN
authors.lastname: Xuan-Huong
authors.forename: J M
authors.initials: JM
authors.lastname: Burgunder
authors.forename: F
authors.initials: F
authors.lastname: Seibold
authors.forename: S
authors.initials: S
authors.lastname: Gallati
authors.forename: H P
authors.initials: HP
authors.lastname: Mattle
mesh_terms: D000328:Adult; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000473:pathology; D004200:Diseases in Twins; D005091:Exons; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology / Q000652:urine; D009154:Mutation; D009431:Neural Conduction / Q000502:physiology; D011877:Radionuclide Imaging; D017422:Sequence Analysis, DNA / Q000379:methods; D035781:Siblings; D013378:Substantia Nigra / Q000000981:diagnostic imaging* / Q000473:pathology; D013936:Thymidine / Q000652:urine; D013939:Thymidine Phosphorylase / Q000235:genetics
chemical_list: D013939:Thymidine Phosphorylase; D013936:Thymidine