title: Biochemical and genetic studies in a family with mitochondrial myopathy.
abstract: We present a family with severe exercise intolerance, progressive proximal weakness, and lactic acidemia. Fifteen of 24 family members in five generations were affected. Since the affected males do not have offspring at this time, the family pedigree is consistent with either maternal or autosomal dominant inheritance. Muscle histochemistry showed ragged-red fibers and electron microscopy showed globular mitochondrial inclusions. Biochemical analysis showed reduced muscle activities of mitochondrial NADH-cytochrome c reductase (1 of 2 patients), succinate-cytochrome c reductase (2 patients), and cytochrome c oxidase (2 patients). For 1 patient, sequence analysis of 44% of the muscle mitochondrial DNA including all 22 transfer RNA regions showed no point mutation with pathogenic significance. Southern blot analysis showed no deletion. Six affected members of the family were treated with methylprednisolone (0.25 mg/kg) for 3 months. Muscle strength, serum lactate, and energy metabolism at rest (measured by 31P magnetic resonance spectroscopy) significantly improved with treatment.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Heiman-Patterson
authors.forename: Z
authors.initials: Z
authors.lastname: Argov
authors.forename: J M
authors.initials: JM
authors.lastname: Chavin
authors.forename: B
authors.initials: B
authors.lastname: Kalman
authors.forename: H
authors.initials: H
authors.lastname: Alder
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
authors.forename: W
authors.initials: W
authors.lastname: Bank
authors.forename: A J
authors.initials: AJ
authors.lastname: Tahmoush
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008854:Microscopy, Electron; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009132:Muscles / Q000201:enzymology / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic
chemical_list: D004272:DNA, Mitochondrial; D005938:Glucocorticoids; D008775:Methylprednisolone