title: Clinicopathological aspects of the neuropathy of neurogastrointestinal encephalomyopathy (MNGIE) in four patients including two with a Charcot-Marie-Tooth presentation.
abstract: We report on four patients with severe polyneuropathy associated with intestinal pseudoobstruction (MNGIE). Three patients presented characteristic supranuclear ophthalmoplegia, and hyperdense signals on T2 weighted cerebral MRI and dystrophic mitochondria in Schwann cells and in endothelial cells in nerve biopsy specimens. Two of these patients had a Charcot-Marie-Tooth (CMT) presentation. All three were heterozygous for a recessively transmitted double substitution in the TP gene: Glu286Lys/Glu289Ala, Asp156Gly/Leu177Pro and Glu289Ala/Gly387Asp. The fourth patient, who was the only patient of this series with an affected sib, had no oculomotor manifestations, nor T2 hyperdense signals on brain MRI, and no TP gene mutation and or morphological abnormalities of mitochondria on electron microscopic examination. He was the only patient of this series with an affected sib. The three patients with the full MNGIE syndrome died before the age of 30 years. Detailed results of nerve pathology show that severe axonal degeneration is associated with segmental abnormalities of the myelin sheath in this syndrome which appears genetically heterogeneous. Our findings suggest that only ophthalmoplegia and hyperdense signals on cerebral MRI are directly related to the mitochondriopathy.
authors.affiliation: Service de Neurologie, Centre Hospitalier Universitaire de Bicêtre, 94275 Le Kremlin Bicêtre, France. gerard.said@bct.ap-hop-paris.fr
authors.forename: Gérard
authors.initials: G
authors.lastname: Said
authors.forename: Catherine
authors.initials: C
authors.lastname: Lacroix
authors.forename: Violaine
authors.initials: V
authors.lastname: Planté-Bordeneuve
authors.forename: Bernard
authors.initials: B
authors.lastname: Messing
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Slama
authors.forename: Pascal
authors.initials: P
authors.lastname: Crenn
authors.forename: Annie
authors.initials: A
authors.lastname: Nivelon-Chevallier
authors.forename: Laurent
authors.initials: L
authors.lastname: Bedenne
authors.forename: Pierre
authors.initials: P
authors.lastname: Soichot
authors.forename: E
authors.initials: E
authors.lastname: Manceau
authors.forename: Daniel
authors.initials: D
authors.lastname: Rigaud
authors.forename: Anne
authors.initials: A
authors.lastname: Guiochon-Mantel
authors.forename: Claude
authors.initials: C
authors.lastname: Matuchansky
mesh_terms: D000328:Adult; D001706:Biopsy / Q000379:methods; D002531:Cerebellum / Q000473:pathology; D002607:Charcot-Marie-Tooth Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005767:Gastrointestinal Diseases / Q000150:complications / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D017237:Mitochondrial Encephalomyopathies / Q000150:complications / Q000235:genetics / Q000473:pathology*; D009132:Muscles / Q000473:pathology; D009154:Mutation; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000648:ultrastructure; D009431:Neural Conduction / Q000502:physiology; D012189:Retrospective Studies; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism
chemical_list: D013939:Thymidine Phosphorylase
references.citation: Neurology. 2002 Aug 13;59(3):455-7
references.pmid: 12177387
references.citation: Ann Neurol. 1990 Sep;28(3):349-60
references.pmid: 2173474
references.citation: Neurologist. 2004 Jan;10(1):8-17
references.pmid: 14720311
references.citation: Rev Neurol (Paris). 1997 Oct;153(10):547-53
references.pmid: 9684018
references.citation: Ann Neurol. 2000 Jun;47(6):792-800
references.pmid: 10852545
references.citation: Acta Neuropathol. 1987;74(3):248-58
references.pmid: 2823522
references.citation: Muscle Nerve. 2004 Mar;29(3):364-8
references.pmid: 14981734
references.citation: Neurology. 1998 Jan;50(1):99-106
references.pmid: 9443465
references.citation: Neurology. 1994 Apr;44(4):721-7
references.pmid: 8164833
references.citation: Neurology. 1998 Oct;51(4):1086-92
references.pmid: 9781534
references.citation: Ann Neurol. 1988 May;23(5):461-5
references.pmid: 2839104