title: Possible toxicity of tuberculostatic agents in a patient with a novel TYMP mutation leading to mitochondrial neurogastrointestinal encephalomyopathy.
abstract: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive multisystemic disorder caused by TYMP gene mutations. Here, we report on the first MNGIE patient diagnosed in Bulgaria who carries a novel homozygous TYMP mutation (p.Leu347Pro). The patient presented with gastrointestinal complaints, cachexia, hearing loss, ptosis, ophthalmoparesis, polyneuropathy, cognitive impairment, and leukoencephalopathy on magnetic resonance imaging (MRI) examination of the brain. The patient's motor capacity declined significantly, leading to wheelchair dependence several months following administration of tuberculostatic treatment, suggesting mitochondrial toxicity of these agents. The advanced stage of the disease and the poor medical condition prevented us from performing allogenic hematopoietic stem cell transplantation (HSCT). Early diagnosis is important not only for genetic counseling but also in view of the timely treatment with allogenic HSCT.
authors.affiliation: Department of Neurology, University Hospital Alexandrovska, 1000 Sofia, Bulgaria. violetamihaylova@yahoo.com
authors.forename: Violeta
authors.initials: V
authors.lastname: Mihaylova
authors.forename: Velina
authors.initials: V
authors.lastname: Guergueltcheva
authors.forename: Sylvia
authors.initials: S
authors.lastname: Cherninkova
authors.forename: Luchezar
authors.initials: L
authors.lastname: Penev
authors.forename: Galina
authors.initials: G
authors.lastname: Georgieva
authors.forename: Katya
authors.initials: K
authors.lastname: Stoyanova
authors.forename: Albenaa
authors.initials: A
authors.lastname: Todorova
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Tournev
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000633:toxicity*; D002031:Bulgaria; D002552:Cerebral Ventricles / Q000473:pathology; D004252:DNA Mutational Analysis; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D013939:Thymidine Phosphorylase / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D013939:Thymidine Phosphorylase