{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T10:51:56Z","timestamp":1775645516628,"version":"3.50.1"},"reference-count":85,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T00:00:00Z","timestamp":1665187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>COQ8A-ataxia is a mitochondrial disease in which a defect in coenzyme Q10 synthesis leads to dysfunction of the respiratory chain. The disease is usually present as childhood-onset progressive ataxia with developmental regression and cerebellar atrophy. However, due to variable phenotype, it may be hard to distinguish from other mitochondrial diseases and a wide spectrum of childhood-onset cerebellar ataxia. COQ8A-ataxia is a potentially treatable condition with the supplementation of coenzyme Q10 as a main therapy; however, even 50% may not respond to the treatment. In this study we review the clinical manifestation and management of COQ8A-ataxia, focusing on current knowledge of coenzyme Q10 supplementation and approach to further therapies. Moreover, the case of a 22-month-old girl with cerebellar ataxia and developmental regression will be presented.<\/jats:p>","DOI":"10.3390\/metabo12100955","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T04:00:02Z","timestamp":1665288002000},"page":"955","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["COQ8A-Ataxia as a Manifestation of Primary Coenzyme Q Deficiency"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1794-8546","authenticated-orcid":false,"given":"Justyna","family":"Paprocka","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5483-3193","authenticated-orcid":false,"given":"Magdalena","family":"Nowak","sequence":"additional","affiliation":[{"name":"Students\u2019 Scientific Society, Department of Pediatric Neurology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Chuchra","sequence":"additional","affiliation":[{"name":"Students\u2019 Scientific Society, Department of Pediatric Neurology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-9549","authenticated-orcid":false,"given":"Robert","family":"\u015amigiel","sequence":"additional","affiliation":[{"name":"Department of Family and Pediatric Nursing, Wroclaw Medical University, 51-618 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1212\/01.wnl.0000438224.25600.6c","article-title":"Prevalence of Ataxia in Children: A Systematic Review","volume":"82","author":"Musselman","year":"2014","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/ana.25751","article-title":"Clinico-Genetic, Imaging and Molecular Delineation of COQ8A-Ataxia: A Multicenter Study of 59 Patients","volume":"88","author":"Schirinzi","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.biochi.2013.12.006","article-title":"The Molecular Genetics of Coenzyme Q Biosynthesis in Health and Disease","volume":"100","author":"Laredj","year":"2014","journal-title":"Biochimie"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1001\/archneurol.2012.206","article-title":"Heterogeneity of Coenzyme Q10 Deficiency: Patient Study and Literature Review","volume":"69","author":"Emmanuele","year":"2012","journal-title":"Arch. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ajhg.2007.12.022","article-title":"CABC1 Gene Mutations Cause Ubiquinone Deficiency with Cerebellar Ataxia and Seizures","volume":"82","author":"Mollet","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10048-019-00597-y","article-title":"Childhood-Onset Autosomal Recessive Ataxias: A Cross-Sectional Study from Turkey","volume":"21","year":"2020","journal-title":"Neurogenetics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jns.2006.01.021","article-title":"Cerebellar Ataxia with Coenzyme Q10 Deficiency: Diagnosis and Follow-up after Coenzyme Q10 Supplementation","volume":"246","author":"Artuch","year":"2006","journal-title":"J. Neurol. Sci."},{"key":"ref_8","first-page":"1","article-title":"Primary CoQ 10 Deficiency with a Severe Phenotype Due to the c.901 C > T (p.R301W) Mutation in the COQ8A Gene","volume":"4","year":"2022","journal-title":"Int. J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/8904_2017_73","article-title":"Compound Heterozygous Inheritance of Mutations in Coenzyme Q8A Results in Autosomal Recessive Cerebellar Ataxia and Coenzyme Q10 Deficiency in a Female Sib-Pair","volume":"42","author":"Jacobsen","year":"2018","journal-title":"JIMD Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.parkreldis.2016.10.010","article-title":"A Novel CABC1\/ADCK3 Mutation in Adult-Onset Cerebellar Ataxia","volume":"33","author":"Malgireddy","year":"2016","journal-title":"Park. Relat. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1007\/s11064-019-02786-5","article-title":"Primary Coenzyme Q Deficiency Due to Novel ADCK3 Variants, Studies in Fibroblasts and Review of Literature","volume":"44","author":"Shalata","year":"2019","journal-title":"Neurochem. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1111\/ene.13003","article-title":"ADCK3 Mutations with Epilepsy, Stroke-like Episodes and Ataxia: A POLG Mimic?","volume":"23","author":"Hikmat","year":"2016","journal-title":"Eur. J. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/cge.12742","article-title":"Cerebellar Ataxia and Severe Muscle CoQ10 Deficiency in a Patient with a Novel Mutation in ADCK3","volume":"90","author":"Barca","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1007\/s12031-022-01993-0","article-title":"Epilepsia Partialis Continua a Clinical Feature of a Missense Variant in the ADCK3 Gene and Poor Response to Therapy","volume":"72","author":"Ashrafi","year":"2022","journal-title":"J. Mol. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40673-019-0109-2","article-title":"One-Year Outcome of Coenzyme Q10 Supplementation in ADCK3 Ataxia (ARCA2)","volume":"6","author":"Schirinzi","year":"2019","journal-title":"Cerebellum Ataxias"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/mdc3.12667","article-title":"ADCK3-Related Coenzyme Q10 Deficiency: A Potentially Treatable Genetic Disease","volume":"5","author":"Chang","year":"2018","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1136\/jnnp-2013-306483","article-title":"Autosomal-Recessive Cerebellar Ataxia Caused by a Novel ADCK3 Mutation That Elongates the Protein: Clinical, Genetic and Biochemical Characterisation","volume":"85","author":"Liu","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/8904_2013_251","article-title":"Heterozygous Mutations in the ADCK3 Gene in Siblings with Cerebellar Atrophy and Extreme Phenotypic Variability","volume":"12","author":"Blumkin","year":"2013","journal-title":"JIMD Reports"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.gene.2019.05.016","article-title":"Exome Sequencing Found a Novel Homozygous Deletion in ADCK3 Gene Involved in Autosomal Recessive Spinocerebellar Ataxia","volume":"708","author":"Hajjari","year":"2019","journal-title":"Gene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.mito.2010.05.008","article-title":"Nonsense Mutations in CABC1\/ADCK3 Cause Progressive Cerebellar Ataxia and Atrophy","volume":"10","author":"Gerards","year":"2010","journal-title":"Mitochondrion"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/s41436-018-0007-7","article-title":"Targeted Exome Analysis Identifies the Genetic Basis of Disease in over 50% of Patients with a Wide Range of Ataxia-Related Phenotypes","volume":"21","author":"Sun","year":"2019","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s40035-021-00264-z","article-title":"Genetic Spectrum and Clinical Features in a Cohort of Chinese Patients with Autosomal Recessive Cerebellar Ataxias","volume":"10","author":"Cheng","year":"2021","journal-title":"Transl. Neurodegener."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s10048-020-00624-3","article-title":"Familial Writer\u2019s Cramp: A Clinical Clue for Inherited Coenzyme Q10 Deficiency","volume":"22","author":"Amprosi","year":"2021","journal-title":"Neurogenetics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.parkreldis.2020.04.003","article-title":"Increased Diagnostic Yield in Complex Dystonia through Exome Sequencing","volume":"74","author":"Wirth","year":"2020","journal-title":"Park. Relat. Disord."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.parkreldis.2020.09.013","article-title":"Homozygosity Mapping and next Generation Sequencing for the Genetic Diagnosis of Hereditary Ataxia and Spastic Paraplegia in Consanguineous Families","volume":"80","author":"Jiao","year":"2020","journal-title":"Park. Relat. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.parkreldis.2019.09.015","article-title":"Dystonia-Ataxia with Early Handwriting Deterioration in COQ8A Mutation Carriers: A Case Series and Literature Review","volume":"68","author":"Galosi","year":"2019","journal-title":"Park. Relat. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1136\/jnnp-2011-301258","article-title":"Adult-Onset Cerebellar Ataxia Due to Mutations in CABC1\/ADCK3","volume":"83","author":"Horvath","year":"2012","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1684\/epd.2021.1243","article-title":"Photoparoxysmal Response in ADCK3 Autosomal Recessive Ataxia: A Case Report and Literature Review","volume":"23","author":"Uccella","year":"2021","journal-title":"Epileptic Disord."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.ajhg.2007.12.024","article-title":"ADCK3, an Ancestral Kinase, Is Mutated in a Form of Recessive Ataxia Associated with Coenzyme Q10 Deficiency","volume":"82","author":"Tazir","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ejpn.2011.07.016","article-title":"The Use of Muscle Biopsy in the Diagnosis of Undefined Ataxia with Cerebellar Atrophy in Children","volume":"16","author":"Terracciano","year":"2012","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/cge.13489","article-title":"A Study in a Polish Ataxia Cohort Indicates Genetic Heterogeneity and Points to MTCL1 as a Novel Candidate Gene","volume":"95","author":"Krygier","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/1750-1172-8-173","article-title":"Phenotypic Variability in ARCA2 and Identification of a Core Ataxic Phenotype with Slow Progression","volume":"8","author":"Mignot","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1420","DOI":"10.1002\/mgg3.1420","article-title":"Primary Coenzyme Q10 Deficiency Due to COQ8A Gene Mutations","volume":"8","author":"Zhang","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.clinbiochem.2020.06.010","article-title":"A Novel COQ8A Missense Variant Associated with a Mild Form of Primary Coenzyme Q10 Deficiency Type 4","volume":"84","author":"Liu","year":"2020","journal-title":"Clin. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/jmd2.12107","article-title":"Early-Onset Coenzyme Q10 Deficiency Associated with Ataxia and Respiratory Chain Dysfunction Due to Novel Pathogenic COQ8A Variants, Including a Large Intragenic Deletion","volume":"54","author":"Cotta","year":"2020","journal-title":"JIMD Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1001\/jamaneurol.2017.5121","article-title":"Efficacy of Exome-Targeted Capture Sequencing to Detect Mutations in Known Cerebellar Ataxia Genes","volume":"75","author":"Coutelier","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1159\/000494465","article-title":"COQ8A and MED25 Mutations in a Child with Intellectual Disability, Microcephaly, Seizures, and Spastic Ataxia: Synergistic Effect of Digenic Variants?","volume":"9","author":"Nair","year":"2019","journal-title":"Mol. Syndromol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1212\/01.wnl.0000244435.27645.54","article-title":"Mitochondrial Disease Criteria: Diagnostic Applications in Children","volume":"67","author":"Morava","year":"2006","journal-title":"Neurology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.molcel.2016.06.030","article-title":"Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase Activity","volume":"63","author":"Stefely","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.molcel.2014.11.002","article-title":"Mitochondrial ADCK3 Employs an Atypical Protein Kinase-like Fold to Enable Coenzyme Q Biosynthesis","volume":"57","author":"Stefely","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Oruganty, K., Talevich, E.E., Neuwald, A.F., and Kannan, N. (2016). Identification and Classification of Small Molecule Kinases: Insights into Substrate Recognition and Specificity. BMC Evol. Biol., 16.","DOI":"10.1186\/s12862-015-0576-x"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.nmd.2011.05.001","article-title":"176th ENMC International Workshop: Diagnosis and Treatment of Coenzyme Q10 Deficiency","volume":"22","author":"Rahman","year":"2012","journal-title":"Neuromuscul. Disord."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1177\/0883073812448680","article-title":"Diagnostic Approach to Childhood-Onset Cerebellar Atrophy","volume":"27","author":"Blaser","year":"2012","journal-title":"J. Child Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12934-017-0646-4","article-title":"Cellular Factories for Coenzyme Q10 Production","volume":"16","author":"Lee","year":"2017","journal-title":"Microb. Cell Fact."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"L\u00f3pez, L.C., Quinzii, C.M., Area, E., Naini, A., Rahman, S., Schuelke, M., Salviati, L., DiMauro, S., and Hirano, M. (2010). Treatment of CoQ10 Deficient Fibroblasts with Ubiquinone, CoQ Analogs, and Vitamin C: Time- and Compound-Dependent Effects. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011897"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.tibtech.2007.08.008","article-title":"Current Prospects for the Production of Coenzyme Q10 in Microbes","volume":"25","author":"Cluis","year":"2007","journal-title":"Trends Biotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.nut.2018.05.020","article-title":"Bioavailability of Coenzyme Q10 Supplements Depends on Carrier Lipids and Solubilization","volume":"57","author":"Navas","year":"2019","journal-title":"Nutrition"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Mantle, D., and Dybring, A. (2020). Bioavailability of Coenzyme Q10: An Overview of the Absorption Process and Subsequent Metabolism. Antioxidants, 9.","DOI":"10.3390\/antiox9050386"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.yrtph.2005.12.002","article-title":"Safety Assessment of Coenzyme Q10 (Kaneka Q10) in Healthy Subjects: A Double-Blind, Randomized, Placebo-Controlled Trial","volume":"44","author":"Ikematsu","year":"2006","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1212\/WNL.50.3.793","article-title":"Absorption, Tolerability, and Effects on Mitochondrial Activity of Oral Coenzyme Q10 in Parkinsonian Patients","volume":"50","author":"Shults","year":"1998","journal-title":"Neurology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1001\/archneur.59.10.1541","article-title":"Effects of Coenzyme Q10 in Early Parkinson Disease: Evidence of Slowing of the Functional Decline","volume":"59","author":"Shults","year":"2002","journal-title":"Arch. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.dmpk.2020.08.002","article-title":"Transport via Niemann-Pick C1 Like 1 Contributes to the Intestinal Absorption of Ubiquinone","volume":"35","author":"Nashimoto","year":"2020","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.bbadis.2006.03.004","article-title":"Dose Ranging and Efficacy Study of High-Dose Coenzyme Q10 Formulations in Huntington\u2019s Disease Mice","volume":"1762","author":"Smith","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8892","DOI":"10.1073\/pnas.95.15.8892","article-title":"Coenzyme Q10 Administration Increases Brain Mitochondrial Concentrations and Exerts Neuroprotective Effects","volume":"95","author":"Matthews","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.bbadis.2014.02.008","article-title":"Ubiquinol-10 Ameliorates Mitochondrial Encephalopathy Associated with CoQ Deficiency","volume":"1842","author":"Doerrier","year":"2014","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"949","DOI":"10.3904\/kjim.2020.211","article-title":"Water-Soluble Coenzyme Q10 Provides Better Protection than Lipid-Soluble Coenzyme Q10 in a Rat Model of Chronic Tacrolimus Nephropathy","volume":"36","author":"Cui","year":"2021","journal-title":"Korean J. Intern. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"115444","DOI":"10.1016\/j.indcrop.2022.115444","article-title":"Formulation, Characterization, Pharmacokinetics and Antioxidant Activity Evaluation of Pinus Koraiensis Nuts Oil Based Coenzyme Q10 Loaded Nanoemulsion","volume":"187","author":"Zhang","year":"2022","journal-title":"Ind. Crops Prod."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"113258","DOI":"10.1016\/j.lwt.2022.113258","article-title":"Characterization, Antioxidant Capacity, and Bioaccessibility of Coenzyme Q10 Loaded Whey Protein Nanoparticles","volume":"160","author":"Liu","year":"2022","journal-title":"LWT"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"119315","DOI":"10.1016\/j.ijpharm.2020.119315","article-title":"Bioavailability of Coenzyme Q10 Loaded in an Oleogel Formulation for Oral Therapy: Comparison with a Commercial-Grade Solid Formulation","volume":"582","author":"Contin","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Wainwright, L., Hargreaves, I.P., Georgian, A.R., Turner, C., Dalton, R.N., Abbott, N.J., Heales, S.J.R., and Preston, J.E. (2020). CoQ10 Deficient Endothelial Cell Culture Model for the Investigation of CoQ10 Blood\u2013Brain Barrier Transport. J. Clin. Med., 9.","DOI":"10.3390\/jcm9103236"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1080\/10717544.2022.2100515","article-title":"Optimized Self-Microemulsifying Drug Delivery System Improves the Oral Bioavailability and Brain Delivery of Coenzyme Q 10","volume":"29","author":"Chhitij","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"113224","DOI":"10.1016\/j.biopha.2022.113224","article-title":"Neuroprotective Effects of Coenzyme Q10-Loaded Exosomes Obtained from Adipose-Derived Stem Cells in a Rat Model of Alzheimer\u2019s Disease","volume":"152","author":"Sheykhhasan","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1212\/01.WNL.0000134607.76780.B2","article-title":"Progression despite Replacement of a Myopathic Form of Coenzyme Q10 Defect","volume":"63","author":"Benoist","year":"2004","journal-title":"Neurology"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Su\u00e1rez-Rivero, J.M., Pastor-Maldonado, C.J., Povea-Cabello, S., \u00c1lvarez-C\u00f3rdoba, M., Villal\u00f3n-Garc\u00eda, I., Munuera-Cabeza, M., Su\u00e1rez-Carrillo, A., Talaver\u00f3n-Rey, M., and S\u00e1nchez-Alc\u00e1zar, J.A. (2021). Coenzyme Q10 Analogues: Benefits and Challenges for Therapeutics. Antioxidants, 10.","DOI":"10.3390\/antiox10020236"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6553","DOI":"10.1038\/s41598-019-43014-y","article-title":"Vitamin K2 Cannot Substitute Coenzyme Q10 as Electron Carrier in the Mitochondrial Respiratory Chain of Mammalian Cells","volume":"9","author":"Cerqua","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1242\/dmm.005579","article-title":"A Drosophila Model for Primary Coenzyme Q Deficiency and Dietary Rescue in the Developing Nervous System","volume":"3","author":"Grant","year":"2010","journal-title":"Dis. Model. Mech."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/acn3.486","article-title":"4-Hydroxybenzoic Acid Restores CoQ10 Biosynthesis in Human COQ2 Deficiency","volume":"4","author":"Herebian","year":"2017","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_68","first-page":"3904905","article-title":"Vanillic Acid Restores Coenzyme Q Biosynthesis and ATP Production in Human Cells Lacking COQ6","volume":"2019","author":"Trevisson","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ymgme.2017.05.012","article-title":"Detection of 6-Demethoxyubiquinone in CoQ10 Deficiency Disorders: Insights into Enzyme Interactions and Identification of Potential Therapeutics","volume":"121","author":"Herebian","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1136\/jmedgenet-2015-102986","article-title":"Rescue of Primary Ubiquinone Deficiency Due to a Novel COQ7 Defect Using 2,4\u2013Dihydroxybensoic Acid","volume":"52","author":"Freyer","year":"2015","journal-title":"J. Med. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"670","DOI":"10.15252\/emmm.201404632","article-title":"The Clinical Heterogeneity of Coenzyme Q10 Deficiency Results from Genotypic Differences in the Coq9 Gene","volume":"7","author":"Barca","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/ajmg.a.61983","article-title":"Clinical Spectrum in Multiple Families with Primary COQ10 Deficiency","volume":"185","author":"Hashemi","year":"2021","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3389\/fneur.2020.00267","article-title":"Clinical Characteristics of Early-Onset and Late-Onset Leigh Syndrome","volume":"11","author":"Hong","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1111\/cge.13713","article-title":"Genetic Heterogeneity in Leigh Syndrome: Highlighting Treatable and Novel Genetic Causes","volume":"97","author":"Lee","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/ana.26260","article-title":"Natural History of Leigh Syndrome: A Study of Disease Burden and Progression","volume":"91","author":"Lim","year":"2022","journal-title":"Ann. Neurol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jaapos.2019.05.005","article-title":"Exophthalmos in Kearns-Sayre Syndrome","volume":"23","author":"Tauber","year":"2019","journal-title":"J. Am. Assoc. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"727","DOI":"10.3349\/ymj.2004.45.4.727","article-title":"Kearns-Sayre Syndrome: -3 Case Reports and Review of Clinical Feature","volume":"45","author":"Park","year":"2004","journal-title":"Yonsei Med. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s00431-011-1662-8","article-title":"Classical MERRF Phenotype Associated with Mitochondrial TRNALeu (m.3243A>G) Mutation","volume":"171","author":"Brackmann","year":"2012","journal-title":"Eur. J. Pediatr."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/(SICI)1097-4598(199703)20:3<271::AID-MUS2>3.0.CO;2-8","article-title":"Myoclonus Epilepsy Associated with Ragged-Red Fibers: A G-to-A Mutation at Nucleotide Pair 8363 in Mitochondrial TRNALys in Two Families","volume":"20","author":"Ozawa","year":"1997","journal-title":"Muscle Nerve"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3174\/ajnr.A0865","article-title":"Clinical and Brain MR Imaging Features Focusing on the Brain Stem and Cerebellum in Patients with Myoclonic Epilepsy with Ragged-Red Fibers Due to Mitochondrial A8344G Mutation","volume":"29","author":"Ito","year":"2008","journal-title":"AJNR. Am. J. Neuroradiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"a011395","DOI":"10.1101\/cshperspect.a011395","article-title":"Clinical and Molecular Features of POLG-Related Mitochondrial Disease","volume":"5","author":"Stumpf","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_82","first-page":"428","article-title":"A New Mitochondrial Disease Associated with Mitochondrial DNA Heteroplasmy","volume":"46","author":"Holt","year":"1990","journal-title":"Am. J. Hum. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1136\/jmg.2008.060616","article-title":"NARP Syndrome in a Patient Harbouring an Insertion in the MT-ATP6 Gene That Results in a Truncated Protein","volume":"46","author":"Solano","year":"2008","journal-title":"J. Med. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.gene.2012.12.066","article-title":"A Novel Mitochondrial Mutation m.8989G>C Associated with Neuropathy, Ataxia, Retinitis Pigmentosa\u2014The NARP Syndrome","volume":"515","author":"Duno","year":"2013","journal-title":"Gene"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1136\/jnnp-2013-306748","article-title":"SANDO Syndrome in a Cohort of 107 Patients with CPEO and Mitochondrial DNA Deletions","volume":"86","author":"Hanisch","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatry"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/10\/955\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:48:11Z","timestamp":1760143691000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/10\/955"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,8]]},"references-count":85,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["metabo12100955"],"URL":"https:\/\/doi.org\/10.3390\/metabo12100955","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,8]]}}}