ubiquinone and Syndrome

Fibromyalgia (FM) is a multifactorial syndrome of unknown etiology, characterized by widespread chronic pain and various somatic and psychological manifestations. The management of FM requires a multidisciplinary approach combining both pharmacological and nonpharmacological strategies. Among nonpharmacological strategies, growing evidence suggests a potential beneficial role for nutrition. This review summarizes the possible relationship between FM and nutrition, exploring the available evidence on the effect of dietary supplements and dietary interventions in these patients. Analysis of the literature has shown that the role of dietary supplements remains controversial, although clinical trials with vitamin D, magnesium, iron and probiotics' supplementation show promising results. With regard to dietary interventions, the administration of olive oil, the replacement diet with ancient grains, low-calorie diets, the low FODMAPs diet, the gluten-free diet, the monosodium glutamate and aspartame-free diet, vegetarian diets as well as the Mediterranean diet all appear to be effective in reducing the FM symptoms. These results may suggest that weight loss, together with the psychosomatic component of the disease, should be taken into account. Therefore, although dietary aspects appear to be a promising complementary approach to the treatment of FM, further research is needed to provide the most effective strategies for the management of FM.

Topics: Acetylcarnitine; Ascorbic Acid; Chlorella; Diet, Vegan; Dietary Supplements; Fibromyalgia; Nutrition Therapy; Nutritional Physiological Phenomena; Syndrome; Ubiquinone; Vitamin E

Primary Coenzyme Q deficiencies represent a group of rare conditions caused by mutations in one of the genes required in its biosynthetic pathway at the enzymatic or regulatory level. The associated clinical manifestations are highly heterogeneous and mainly affect central and peripheral nervous system, kidney, skeletal muscle and heart. Genotype-phenotype correlations are difficult to establish, mainly because of the reduced number of patients and the large variety of symptoms. In addition, mutations in the same

Topics: Ataxia; Genotype; Humans; Mitochondrial Diseases; Muscle Weakness; Mutation; Phenotype; Structure-Activity Relationship; Syndrome; Ubiquinone

Topics: Coenzymes; Diagnosis, Differential; Humans; Lactic Acid; Mitochondria; Mitochondrial Diseases; Mitochondrial Encephalomyopathies; Myoglobinuria; Prognosis; Syndrome; Ubiquinone

Three Korean girls with ethylmalonic encephalopathy, the first Asian cases, were identified. In all three cases, we observed slight improvement in motor functions, cognitive behaviours and chronic mucoid diarrhoea after treatment with riboflavin and/or coenzyme Q10 treatment. The precise pathogenesis of ethylmalonic encephalopathy has not been fully elucidated, but riboflavin treatment may be helpful.

Topics: Brain Diseases, Metabolic, Inborn; Child, Preschool; Coenzymes; Cognition; Diarrhea; Electron Transport; Female; Humans; Infant; Korea; Malonates; Motor Skills; Riboflavin; Syndrome; Ubiquinone

Propofol is a short-acting intravenous anesthetic agent. In rare conditions, a life-threatening complication known as propofol infusion syndrome can occur. The pathophysiologic mechanism is still unknown. Some studies suggested that propofol acts as uncoupling agent, others suggested that it inhibits complex I or complex IV, or causes increased oxidation of cytochrome c and cytochrome aa3, or inhibits mitochondrial fatty acid metabolism. Although the exact site of interaction is not known, most hypotheses point to the direction of the mitochondria.. Eight rats were ventilated and sedated with propofol up to 20 h. Sequential biopsy specimens were taken from liver and skeletal muscle and used for determination of respiratory chain activities and propofol concentration. Activities were also measured in skeletal muscle from a patient who died of propofol infusion syndrome.. In rats, authors detected a decrease in complex II+III activity starting at low tissue concentration of propofol (20 to 25 µM), further declining at higher concentrations. Before starting anesthesia, the complex II+III/citrate synthase activity ratio in liver was 0.46 (0.25) and in skeletal muscle 0.23 (0.05) (mean [SD]). After 20 h of anesthesia, the ratios declined to 0.17 (0.03) and 0.12 (0.02), respectively. When measured individually, the activities of complexes II and III remained normal. Skeletal muscle from one patient taken in the acute phase of propofol infusion syndrome also shows a selective decrease in complex II+III activity (z-score: -2.96).. Propofol impedes the electron flow through the respiratory chain and coenzyme Q is the main site of interaction with propofol.

Topics: Anesthetics, Intravenous; Animals; Citric Acid Cycle; Electron Transport; Male; Muscle, Skeletal; Propofol; Rats; Rats, Wistar; Respiration, Artificial; Syndrome; Ubiquinone

Propofol is an anesthetic agent widely used for induction and maintenance of anesthesia, and sedation in children. Although generally considered as reliable and safe, administration of propofol can occasionally induce a potentially fatal complication known as propofol infusion syndrome (PRIS). Mitochondrial dysfunction has been implicated in the pathogenesis of PRIS. We report on an adult patient with Leber hereditary optic neuropathy (LHON) who developed PRIS. He was a carrier of the m.3460G>A mutation, one of the major three pathogenic point mutations associated with LHON. The propositus was blind and underwent propofol sedation after severe head injury. Five days after start of propofol infusion, the patient died. The activity of complex I of the oxidative phosphorylation (OXPHOS) system was severely deficient in skeletal muscle. Our observation indicates that fulminate PRIS can occur in an adult patient with an inborn OXPHOS defect and corroborates the hypothesis that PRIS is caused by inhibition of the OXPHOS system.

Topics: Adult; Anesthetics, Intravenous; Humans; Infusions, Intravenous; Male; Muscle, Skeletal; Optic Atrophy, Hereditary, Leber; Oxidative Phosphorylation; Propofol; Risk Factors; Syndrome; Ubiquinone

Cyclic vomiting syndrome (CVS), which is defined by recurrent stereotypical episodes of nausea and vomiting, is a relatively-common disabling condition that is associated with migraine headache and mitochondrial dysfunction. Co-enzyme Q10 (Co-Q) is a nutritional supplement that has demonstrated efficacy in pediatric and adult migraine. It is increasingly used in CVS despite the complete lack of studies to demonstrate its value in treatment. Using an Internet-based survey filled out by subjects with CVS or their parents, the efficacy, tolerability and subject satisfaction in CVS prophylaxis were queried. Subjects taking Co-Q (22 subjects) were compared against those taking amitriptyline (162 subjects), which is the general standard-of-care.. Subjects/parents reported similar levels of efficacy for a variety of episode parameters (frequency, duration, number of emesis, nausea severity). There was a 50% reduction in at least one of those four parameters in 72% of subjects treated with amitriptyline and 68% of subjects treated Co-Q. However, while no side effects were reported on Co-Q, 50% of subjects on amitriptyline reported side effects (P = 5 x 10-7), resulting in 21% discontinuing treatment (P = 0.007). Subjects/parents considered the benefits to outweigh the risks of treatment in 47% of cases on amitriptyline and 77% of cases on Co-Q (P = 0.008).. Our data suggest that the natural food supplement Co-Q is potentially efficacious and tolerable in the treatment of CVS, and should be considered as an option in CVS prophylaxis. Our data would likely be helpful in the design of a double-blind clinical trial.

Topics: Age of Onset; Amitriptyline; Antiemetics; Humans; Internet; Parents; Patient Satisfaction; Periodicity; Retrospective Studies; Risk Assessment; Syndrome; Treatment Outcome; Ubiquinone; Vomiting

Coenzyme Q10 (CoQ) is a small lipophilic molecule critical for the transport of electrons from complexes I and II to complex III in the mitochondrial respiratory chain. CoQ deficiency is a rare human genetic condition that has been associated with a variety of clinical phenotypes. With the aim of elucidating how CoQ deficiency affects an organism, we have investigated the pathophysiologic processes present within fibroblasts derived from 4 patients with CoQ deficiency. Assays of cultured fibroblasts revealed decreased activities of complex II+III, complex III, and complex IV, reduced expression of mitochondrial proteins involved in oxidative phosphorylation, decreased mitochondrial membrane potential, increased production of reactive oxygen species (ROS), activation of mitochondrial permeability transition (MPT), and reduced growth rates. These abnormalities were partially restored by CoQ supplementation. Moreover, we demonstrate that CoQ deficient fibroblasts exhibited increased levels of lysosomal markers (beta-galactosidase, cathepsin, LC3, and Lyso Tracker), and enhanced expression of autophagic genes at both transcriptional and translational levels, indicating the presence of autophagy. Electron microscopy studies confirmed a massive degradation of the altered mitochondria by mitophagy. Autophagy in CoQ deficient fibroblasts was abolished by antioxidants or cyclosporin treatments suggesting that both ROS and MPT participate in this process. Furthermore, prevention of autophagy in CoQ deficient fibroblasts by 3-methyl adenine or wortmannin, as well as the induction of CoQ deficiency in cells lacking autophagy (by means of genetic knockout of the Atg5 gene in mouse embryonic fibroblasts) resulted in apoptotic cell death, suggesting a protective role of autophagy in CoQ deficiency.

Topics: Animals; Apoptosis; Autophagy; Autophagy-Related Protein 5; Biomarkers; Blotting, Western; Cell Proliferation; Cell Survival; Electron Transport; Fibroblasts; Gene Expression Regulation; Humans; Membrane Potential, Mitochondrial; Mice; Microtubule-Associated Proteins; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Mitochondrial Proteins; Reactive Oxygen Species; RNA, Messenger; Syndrome; Ubiquinone

Coenzyme Q10 (CoQ10 or ubiquinone) is a lipid-soluble component of virtually all cell membranes and has multiple metabolic functions. A major function of CoQ10 is to transport electrons from complexes I and II to complex III in the respiratory chain which resides in the mitochondrial inner membrane. Deficiencies of CoQ10 (MIM 607426) have been associated with four major clinical phenotypes: 1) encephalomyopathy characterized by a triad of recurrent myoglobinuria, brain involvement, and ragged-red fibers; 2) infantile multisystemic disease typically with prominent nephropathy and encephalopathy; 3) cerebellar ataxia with marked cerebellar atrophy; and 4) pure myopathy. Primary CoQ10 deficiencies due to mutations in ubiquinone biosynthetic genes (COQ2, PDSS1, PDSS2, and ADCK3 [CABC1]) have been identified in patients with the infantile multisystemic and cerebellar ataxic phenotypes. In contrast, secondary CoQ10 deficiencies, due to mutations in genes not directly related to ubiquinone biosynthesis (APTX, ETFDH, and BRAF), have been identified in patients with cerebellar ataxia, pure myopathy, and cardiofaciocutaneous syndrome. In many patients with CoQ10 deficiencies, the causative molecular genetic defects remain unknown; therefore, it is likely that mutations in additional genes will be identified as causes of CoQ10 deficiencies.

Topics: Cerebellar Ataxia; Humans; Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Syndrome; Ubiquinone

To study CoQ(10) concentrations in muscle and fibroblast from 6 patients with a CoQ(10) deficiency syndrome.. CoQ(10) was quantified by HPLC with electrochemical detection.. Four out of the 6 cases showed muscle CoQ(10) deficiency plus a reduction of mitochondrial respiratory chain enzyme activities. All cases showed decreased CoQ(10) values in fibroblasts when compared with controls.. Biochemical study of CoQ(10) in both muscle and fibroblasts seems advisable to demonstrate the deficiency in all patients.

Topics: Adolescent; Adult; Biomarkers; Child; Child, Preschool; Electron Transport; Fibroblasts; Humans; Infant; Infant, Newborn; Middle Aged; Mitochondria, Muscle; Muscle, Skeletal; Syndrome; Ubiquinone

The cardiofaciocutaneous (CFC) syndrome is characterized by congenital heart defect, developmental delay, peculiar facial appearance with bitemporal constriction, prominent forehead, downslanting palpebral fissures, curly sparse hair and abnormalities of the skin. CFC syndrome phenotypically overlaps with Noonan and Costello syndromes. Mutations of several genes (PTPN11, HRAS, KRAS, BRAF, MEK1 and MEK2), involved in the mitogen-activated protein kinase (MAPK) pathway, have been identified in CFC-Costello-Noonan patients. Coenzyme Q10 (CoQ10), a lipophilic molecule present in all cell membranes, functions as an electron carrier in the mitochondrial respiratory chain, where it transports electrons from complexes I and II to complex III. CoQ10 deficiency is a rare treatable mitochondrial disorder with various neurological (cerebellar ataxia, myopathy, epilepsy, mental retardation) and extraneurological (cardiomyopathy, nephropathy) signs that are responsive to CoQ10 supplementation. We report the case of a 4-year-old girl who presented a CFC syndrome, confirmed by the presence of a pathogenic R257Q BRAF gene mutation, together with a muscular CoQ10 deficiency. Her psychomotor development was severely impaired, hindered by muscular hypotonia and ataxia, both improving remarkably after CoQ10 treatment. This case suggests that there is a functional connection between the MAPK pathway and the mitochondria. This could be through the phosphorylation of a nuclear receptor essential for CoQ10 biosynthesis. Another hypothesis is that K-Ras, one of the proteins composing the MAPK pathway, might be recruited into the mitochondria to promote apoptosis. This case highlights that CoQ10 might contribute to the pathogenesis of CFC syndrome.

Topics: Abnormalities, Multiple; Child, Preschool; Coenzymes; Craniofacial Abnormalities; Female; Heart Defects, Congenital; Humans; MAP Kinase Signaling System; Mitochondria; Mitochondrial Diseases; Muscle, Skeletal; Skin Abnormalities; Syndrome; Treatment Outcome; Ubiquinone

Sensory ataxia with neuropathy, dysarthria and ophthalmoparesis represent the clinical triad of SANDO, a specific mitochondrial phenotype first reported in 1997 in association with multiple mitochondrial DNA deletions and mutations in POLG1 or more rarely in the C10orf2 (twinkle-helicase) gene. We report a 44-year-old man with SANDO who harboured two novel mutations (P648R/R807C) in the POLG1 gene.

Topics: Acetylcarnitine; Adult; Coenzymes; DNA Mutational Analysis; DNA Polymerase gamma; DNA-Directed DNA Polymerase; Dysarthria; Hereditary Sensory and Autonomic Neuropathies; Humans; Male; Mitochondrial Myopathies; Muscle, Skeletal; Mutation; Ophthalmoplegia; Peripheral Nerves; Syndrome; Ubiquinone

Many CoQ trials for mitochondrial encephalomyopathy are reported, however, the action of CoQ in the central nervous system is unknown. We administered CoQ to a patient with MELAS, and decreasing CSF lactate and pyruvate levels were revealed. This reduction in CSF lactate and pyruvate may be evidence that CoQ acts directly on the CNS. There have been no other descriptions of evidence of CoQ effective action in the central nervous system, a finding unique to this report.

Topics: Acidosis, Lactic; Adult; Agnosia; Cerebrovascular Disorders; Delirium; Dose-Response Relationship, Drug; Hemianopsia; Humans; Lactates; Lactic Acid; Magnetic Resonance Imaging; Male; Mitochondria, Muscle; Neurologic Examination; Neuromuscular Diseases; Pyruvates; Pyruvic Acid; Syndrome; Ubiquinone

Two patients with mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes (MELAS) in one family are reported. Pathological examination of case 1 showed ragged-red fibers, with 7% of the fibers being unstained by cytochrome c oxidase stain, peripheral nerve damage, multiple areas of softening in the cerebrum and midbrain, and spongy changes in the cerebrum, optic nerve and pons. Electron microscopic examination revealed abnormal accumulations of mitochondria in the skeletal muscle, smooth muscle and cardiac muscle. The activity of cytochrome c oxidase in the brain and liver showed a tendency to decrease. In case 2 (maternal aunt of case 1), muscular weakness and peripheral nerve damage improved by treatment with coenzyme Q10. By adding idebenone to the coenzyme Q10 therapy, the EEG and Wechsler's Adult Intelligence Scale (WAIS) improved. Furthermore, in the cerebral spinal fluid (CSF), the protein, lactate, and pyruvate decreased, and the monoamines and monoamine metabolites increased.

Topics: Acidosis, Lactic; Adolescent; Benzoquinones; Brain Diseases; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Mitochondria, Muscle; Quinones; Syndrome; Ubiquinone

Topics: Acidosis, Lactic; Benzoquinones; Brain Diseases, Metabolic; Coenzymes; Female; Humans; Middle Aged; Mitochondria, Muscle; Neuromuscular Diseases; Quinones; Syndrome; Ubiquinone

In a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS] who had normal mitochondrial enzyme activity, high doses of coenzyme Q10 (CoQ) were administered. Clinical improvement with decreased serum lactate and pyruvate levels was observed. Though the mechanism of action of CoQ is not known, a trial is worthwhile in patients with MELAS.

Topics: Acidosis, Lactic; Adolescent; Betamethasone; Brain Diseases; Coenzymes; Female; Humans; Mitochondria, Muscle; Muscular Diseases; Prednisolone; Syndrome; Ubiquinone