title: Mitochondrial myopathy with tRNA(Leu(UUR)) mutation and complex I deficiency responsive to riboflavin.
abstract: Deficiency of complex I (reduced nicotinamide adenine dinucleotide dehydrogenase-ubiquinone oxidoreductase) of the mitochondrial respiratory chain may be seen as a pure myopathy or as a neuromuscular disorder at presentation. Efficacy of long- term therapy for these disorders is yet to be established. We report the case of a female patient with complex I deficiency and skeletal myopathy, who has had a sustained clinical response to riboflavin during 3 years of therapy. Molecular studies found no mutations in the putative flavin mononucleotide binding site in the 51 kd subunit of complex I, but a T-to-C transition at nucleotide 3250 in the mitochondrial DNA tRNA(Leu(UUR)) gene was identified. This mutation has been reported in one other family in that five members had fatigue with or without muscle weakness. There were also five cases of unexplained infant deaths in that family and two cases in the family reported here. Riboflavin therapy should be attempted in all patients with complex I deficiency when the clinical presentation is one of isolated skeletal myopathy.
authors.affiliation: Department of Medical Genetics, Royal Alexandra Hospital for Children, Westmead, New South Wales, Australia.
authors.forename: R F
authors.initials: RF
authors.lastname: Ogle
authors.forename: J
authors.initials: J
authors.lastname: Christodoulou
authors.forename: E
authors.initials: E
authors.lastname: Fagan
authors.forename: R B
authors.initials: RB
authors.lastname: Blok
authors.forename: D M
authors.initials: DM
authors.lastname: Kirby
authors.forename: K L
authors.initials: KL
authors.lastname: Seller
authors.forename: H H
authors.initials: HH
authors.lastname: Dahl
authors.forename: D R
authors.initials: DR
authors.lastname: Thorburn
mesh_terms: D002331:Carnitine / Q000627:therapeutic use; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D017240:Mitochondrial Myopathies / Q000188:drug therapy* / Q000235:genetics; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency*; D010375:Pedigree; D017354:Point Mutation; D012343:RNA, Transfer / Q000235:genetics; D012256:Riboflavin / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial; D012343:RNA, Transfer; D016660:NAD(P)H Dehydrogenase (Quinone); D002331:Carnitine; D012256:Riboflavin