ubiquinone and Chromosome-Deletion

Forty-four patients with mitochondrial myopathies were treated with Ubidecarenone (CoQ10) for 6 months in an open multi-center trial. No side effects of the drug were observed. Sixteen patients showing at least 25% decrease of post-exercise lactate levels were selected as responders. Responsiveness was apparently not related to CoQ10 level in serum and platelets or to the presence or absence of mtDNA deletions. The responders were treated for a further 3 months with CoQ10 or placebo in the second blind part of the trial; no significant differences were observed between the 2 groups. It is not clear why CoQ10 had therapeutic effects in some patients and not in others with the same clinical presentation and biochemical defect, and we failed to identify candidate responders before treatment. At the dose of CoQ10 used in this study (2 mg/kg/day) the therapy requires a long administration time before a response is seen.

Topics: Blood Platelets; Chromosome Deletion; Coenzymes; DNA, Mitochondrial; Double-Blind Method; Female; Humans; Lactates; Lactic Acid; Male; Mitochondria; Mitochondria, Muscle; Muscles; Muscular Diseases; Physical Exertion; Ubiquinone

The main symptom of chronic progressive external ophthalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS) are upper eyelid ptosis and a slowly progressive weakness of the extraocular muscles. Mitochondrial disorders are much more frequent than previously assumed. Because of great phenotypic variability, early diagnosis may prove to be difficult.. Retrospective analysis of 30 patients with CPEO or KSS with regard to ophthalmological and neurological findings as well as molecular genetic background.. Twenty-seven patients presented with upper eyelid ptosis as the first clinical symptom. In 11 of these patients, ptosis was either unilateral or asymmetric. External ophthalmoplegia was present in only three patients initially; however, it developed in 27 patients in the later course of the disease. Diplopia was found to be more frequent than previously assumed. Twenty-six patients showed characteristic histological hallmarks in skeletal muscle biopsy. In 22 patients, molecular genetic testing revealed mitochondrial DNA mutations.. Mitochondrial disorders should be included in the early differential diagnosis of patients with etiologically unclear acquired isolated unilateral or bilateral ptosis, atypical eye movement disorders, or diplopia. A correct diagnosis is mandatory for qualified counseling and the management of potentially life-threatening complications, such as cardiac involvement.

Topics: Adolescent; Adult; Age of Onset; Aged; Aged, 80 and over; Blepharoptosis; Child; Chromosome Deletion; Combined Modality Therapy; DNA, Mitochondrial; Female; Gene Rearrangement; Hearing Aids; Humans; Kearns-Sayre Syndrome; Male; Middle Aged; Neurologic Examination; Ophthalmoplegia, Chronic Progressive External; Pacemaker, Artificial; Patient Care Team; Point Mutation; Polymorphism, Restriction Fragment Length; Retrospective Studies; Ubiquinone

The cytochrome d terminal oxidase complex is one of two terminal oxidases in the aerobic respiratory chain of Escherichia coli. The enzyme is located in the cytoplasmic membrane where it oxidizes ubiquinol-8 in the bilayer and reduces oxygen to water. Enzyme turnover is coupled to the generation of a proton-motive force, resulting in electrogenic translocation across the membrane of one proton per electron passing through the system. The enzyme is an alpha beta heterodimer containing four hemes. The cyd locus, encoding both subunits, has previously been genetically mapped and cloned. This work describes an insertion and deletion analysis of cyd which indicates the direction of transcription, defines the coding regions, and suggests that cyd is an operon. In addition, the complete DNA sequence of the cyd gene is reported. Two open reading frames, separated by 18 base pairs, encode the two subunits of the oxidase complex. Hydropathy profiles of the deduced protein sequence indicate that subunits I and II are each likely to have multiple transmembrane elements. There are only 10 histidines in both subunits, several of which are likely to serve as heme axial ligands.

Topics: Amino Acid Sequence; Base Sequence; Chromosome Deletion; Chromosome Mapping; Cloning, Molecular; Cytochrome b Group; Cytochromes; DNA Restriction Enzymes; Electron Transport Chain Complex Proteins; Escherichia coli; Escherichia coli Proteins; Intracellular Membranes; Macromolecular Substances; Molecular Sequence Data; Oxidation-Reduction; Oxidoreductases; Oxygen; Ubiquinone