title: Recurrent myoglobinuria in a sporadic patient with a novel mitochondrial DNA tRNA(Ile) mutation.
abstract: The differential diagnosis of myoglobinuria includes multiple etiologies, such as infection, inflammation, trauma, endocrinopathies, drugs toxicity, and primary metabolic disorders. Metabolic myopathies can be due to inherited disorders of glycogen metabolism or to defects of fatty acid oxidation. Primary respiratory chain dysfunction is a rare cause of myoglobinuria, but it has been described in sporadic cases with mutations in genes encoding cytochrome b or cytochrome c oxidase (COX) subunits and in four cases with tRNA mutations. We describe a 39-year-old woman with myalgia and exercise-related recurrent myoglobinuria, who harbored a novel mitochondrial DNA mutation at nucleotide 4281 (m.4281A>G) in the tRNA-isoleucine gene. Her muscle biopsy revealed ragged-red and COX-deficient fibers. No deletions or duplication were detected by Southern blot analysis. The m.4281A>G mutation was present in the patient's muscle with a mutation load of 46% and was detected in trace amounts in urine and cheek mucosa. Single-fiber analysis revealed significantly higher levels of the mutation in COX-deficient (65%) than in normal fibers (45%). This novel mutation has to be added to the molecular causes of recurrent myoglobinuria.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Emmanuele
authors.forename: Evangelia
authors.initials: E
authors.lastname: Sotiriou
authors.forename: Maryam
authors.initials: M
authors.lastname: Shirazi
authors.forename: Kurenai
authors.initials: K
authors.lastname: Tanji
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Haller
authors.forename: Katja
authors.initials: K
authors.lastname: Heinicke
authors.forename: Peter E
authors.initials: PE
authors.lastname: Bosch
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D003402:Creatine Kinase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000378:metabolism; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D005260:Female; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009212:Myoglobinuria / Q000209:etiology* / Q000235:genetics*; D009690:Nucleic Acid Conformation; D010146:Pain / Q000209:etiology; D012355:RNA, Transfer, Ile / Q000235:genetics*; D012206:Rhabdomyolysis / Q000150:complications* / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D012355:RNA, Transfer, Ile; D003576:Electron Transport Complex IV; D003402:Creatine Kinase